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1. Radujkovic A, Topaly J, Fruehauf S, Zeller WJ: Combination treatment of imatinib-sensitive and -resistant BCR-ABL-positive CML cells with imatinib and farnesyltransferase inhibitors. Anticancer Res; 2006 May-Jun;26(3A):2169-77
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  • [Title] Combination treatment of imatinib-sensitive and -resistant BCR-ABL-positive CML cells with imatinib and farnesyltransferase inhibitors.
  • BACKGROUND: Resistance to imatinib monotherapy frequently emerges in advanced stages of chronic myelogenous leukemia (CML), supporting the rationale for combination drug therapy.
  • In the present study, the activities of the farnesyltransferase inhibitors (FTIs) L744,832 and LB42918, as single agents and in combination with imatinib, were investigated in different imatinib-sensitive and -resistant BCR-ABL-positive CML cells.
  • Drug interactions were analyzed according to the median-effect method of Chou and Talalay.
  • In primary chronic phase CML cells, additive and synergistic effects were discernible for the combination of imatinib plus L744,832 and imatinib plus LB42918, respectively.
  • Annexin V/propidium iodide staining showed enhancement of imatinib-induced apoptosis with either drug combination, both in imatinib-sensitive and -resistant cells.
  • CONCLUSION: The results indicated the potential of L744,832 and LB42918 as combination agents for CML patients on imatinib treatment.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / pharmacology. Enzyme Inhibitors / pharmacology. Farnesyltranstransferase / antagonists & inhibitors. Fusion Proteins, bcr-abl / biosynthesis. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / metabolism
  • [MeSH-minor] Apoptosis / drug effects. Benzamides. Cell Growth Processes / drug effects. Cell Line, Tumor. Humans. Imatinib Mesylate. K562 Cells. Methionine / administration & dosage. Methionine / analogs & derivatives. Methionine / pharmacology. P-Glycoprotein / metabolism. Piperazines / administration & dosage. Pyrimidines / administration & dosage

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  • (PMID = 16827161.001).
  • [ISSN] 0250-7005
  • [Journal-full-title] Anticancer research
  • [ISO-abbreviation] Anticancer Res.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] Greece
  • [Chemical-registry-number] 0 / Benzamides; 0 / Enzyme Inhibitors; 0 / L 744832; 0 / P-Glycoprotein; 0 / Piperazines; 0 / Pyrimidines; 8A1O1M485B / Imatinib Mesylate; AE28F7PNPL / Methionine; EC 2.5.1.29 / Farnesyltranstransferase; EC 2.7.10.2 / Fusion Proteins, bcr-abl
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2. Fischer T, Reifenrath C, Hess GR, Corsetti MT, Kreil S, Beck J, Meinhardt P, Beltrami G, Schuch B, Gschaidmeier H, Hehlmann R, Hochhaus A, Carella A, Huber C: Safety and efficacy of STI-571 (imatinib mesylate) in patients with bcr/abl-positive chronic myelogenous leukemia (CML) after autologous peripheral blood stem cell transplantation (PBSCT). Leukemia; 2002 Jul;16(7):1220-8
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  • [Title] Safety and efficacy of STI-571 (imatinib mesylate) in patients with bcr/abl-positive chronic myelogenous leukemia (CML) after autologous peripheral blood stem cell transplantation (PBSCT).
  • We examined safety and efficacy of STI-571 in 24 bcr/abl-positive patients with CML post PBSCT.
  • At start of STI-571 therapy, nine patients presented in blast crisis (BC) or in accelerated phase (AP), and 15 in chronic phase (CP).
  • In general, STI-571 was well tolerated in this heavily pretreated group of patients with a non-hematologic and hematologic toxicity profile similar to that observed in a previous phase I trial at comparable doses.
  • Five of nine patients with CML in transformation (AP, BC) were evaluable for hematologic response.
  • In CML chronic phase, STI-571 induced complete hematologic responses in all patients and major cytogenetic responses in 61% of patients with a complete cytogenetic response rate of 46%.
  • This report indicates that STI-571 is a safe and effective drug in heavily pretreated patients.
  • The high rate of complete hematologic and complete cytogenetic responses in CP patients is remarkable, as intensive treatment approaches plus IFN-alpha failed to be efficient in achieving long-term stabilization of CML in this patient cohort.
  • [MeSH-major] Antineoplastic Agents / administration & dosage. Fusion Proteins, bcr-abl / antagonists & inhibitors. Hematopoietic Stem Cell Transplantation. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / therapy. Piperazines / administration & dosage. Pyrimidines / administration & dosage
  • [MeSH-minor] Adult. Benzamides. Blood Cell Count. Combined Modality Therapy. Enzyme Inhibitors / administration & dosage. Enzyme Inhibitors / adverse effects. Female. Humans. Imatinib Mesylate. Male. Middle Aged. Protein-Tyrosine Kinases / antagonists & inhibitors. Transplantation, Autologous. Treatment Outcome

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  • (PMID = 12094246.001).
  • [ISSN] 0887-6924
  • [Journal-full-title] Leukemia
  • [ISO-abbreviation] Leukemia
  • [Language] eng
  • [Publication-type] Clinical Trial; Clinical Trial, Phase II; Journal Article; Multicenter Study; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Benzamides; 0 / Enzyme Inhibitors; 0 / Piperazines; 0 / Pyrimidines; 8A1O1M485B / Imatinib Mesylate; EC 2.7.10.1 / Protein-Tyrosine Kinases; EC 2.7.10.2 / Fusion Proteins, bcr-abl
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3. von Bubnoff N, Duyster J: Chronic myelogenous leukemia: treatment and monitoring. Dtsch Arztebl Int; 2010 Feb;107(7):114-21
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  • [Title] Chronic myelogenous leukemia: treatment and monitoring.
  • BACKGROUND: The treatment options for bcr-abl positive chronic myelogenous leukemia (CML) include chemotherapy, immune therapy, allogeneic stem cell transplantation, and molecular therapy.
  • The tyrosine kinase inhibitor imatinib was approved for the treatment of CML in 2002.
  • Data from clinical trials allow a comparison of treatment options.
  • METHODS: The literature on the treatment and monitoring of CML was selectively reviewed.
  • RESULTS: In a clinical phase 3 trial of imatinib treatment for patients in the chronic phase of CML, the rates of progression-free and overall survival at 6 years were 93% and 88%, respectively.
  • One in four patients in the chronic phase of CML has an inadequate cytogenetic response to imatinib and therefore requires a change of treatment.
  • Most imatinib-resistant patients in the chronic phase of CML go into remission again after switching to one of the new tyrosine kinase inhibitors, dasatinib and nilotinib.
  • CONCLUSION: Imatinib is now the standard initial first-line treatment for CML in the chronic phase.
  • Regular hematologic and cytogenetic monitoring during treatment is indispensable so that patients with an inadequate response can be identified.
  • [MeSH-major] Leukemia, Myelogenous, Chronic, BCR-ABL Positive / mortality. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / therapy. Piperazines / therapeutic use. Pyrimidines / therapeutic use. Stem Cell Transplantation / mortality. Stem Cell Transplantation / statistics & numerical data
  • [MeSH-minor] Benzamides. Humans. Imatinib Mesylate. Prevalence. Risk Assessment. Risk Factors. Survival Analysis. Survival Rate. Treatment Outcome

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  • [Cites] J Clin Oncol. 1999 Jun;17(6):1858-68 [10561226.001]
  • [Cites] J Natl Cancer Inst. 2000 Oct 18;92(20):1641-50 [11036109.001]
  • [Cites] N Engl J Med. 2001 Apr 5;344(14):1038-42 [11287973.001]
  • [Cites] Science. 2001 Aug 3;293(5531):876-80 [11423618.001]
  • [Cites] Blood. 2001 Nov 15;98(10):3074-81 [11698293.001]
  • [Cites] Blood. 2001 Dec 15;98(13):3569-74 [11739158.001]
  • [Cites] Lancet. 2002 Feb 9;359(9305):487-91 [11853795.001]
  • [Cites] Blood. 2002 Mar 1;99(5):1527-35 [11861264.001]
  • [Cites] Blood. 2002 Mar 15;99(6):1928-37 [11877262.001]
  • [Cites] Blood. 2002 May 1;99(9):3472-5 [11964322.001]
  • [Cites] Blood. 2002 May 15;99(10):3530-9 [11986204.001]
  • [Cites] Blood. 2002 May 15;99(10):3547-53 [11986206.001]
  • [Cites] Clin Cancer Res. 2002 Jul;8(7):2167-76 [12114417.001]
  • [Cites] Blood. 2002 Aug 1;100(3):1014-8 [12130516.001]
  • [Cites] Blood. 2002 Sep 15;100(6):1965-71 [12200353.001]
  • [Cites] Cancer Cell. 2002 Aug;2(2):117-25 [12204532.001]
  • [Cites] Leukemia. 2002 Nov;16(11):2190-6 [12399961.001]
  • [Cites] Blood. 2003 Jan 15;101(2):473-5 [12393385.001]
  • [Cites] N Engl J Med. 2003 Mar 13;348(11):994-1004 [12637609.001]
  • [Cites] Haematologica. 2003 Mar;88(3):260-7 [12651263.001]
  • [Cites] J Clin Oncol. 2003 Apr 15;21(8):1637-47 [12668652.001]
  • [Cites] Blood. 2003 May 15;101(10):3794-800 [12560227.001]
  • [Cites] Clin Cancer Res. 2003 Jun;9(6):2092-7 [12796373.001]
  • [Cites] Leukemia. 2003 Aug;17(8):1529-37 [12886239.001]
  • [Cites] N Engl J Med. 2003 Oct 9;349(15):1423-32 [14534335.001]
  • [Cites] N Engl J Med. 2003 Oct 9;349(15):1451-64 [14534339.001]
  • [Cites] Leuk Res. 2004 May;28 Suppl 1:S71-3 [15036945.001]
  • [Cites] Br J Haematol. 2004 Jun;125(5):613-20 [15147377.001]
  • [Cites] Science. 2004 Jul 16;305(5682):399-401 [15256671.001]
  • [Cites] Leukemia. 2004 Aug;18(8):1321-31 [15215876.001]
  • [Cites] Blood. 2004 Oct 1;104(7):2204-5 [15377577.001]
  • [Cites] N Engl J Med. 1986 Apr 24;314(17):1065-9 [3457264.001]
  • [Cites] Cancer. 1988 Apr 1;61(7):1441-6 [3162181.001]
  • [Cites] Science. 1990 Feb 16;247(4944):824-30 [2406902.001]
  • [Cites] Science. 1990 Mar 2;247(4946):1079-82 [2408149.001]
  • [Cites] Blood. 1994 Dec 15;84(12):4064-77 [7994025.001]
  • [Cites] Nat Med. 1996 May;2(5):561-6 [8616716.001]
  • [Cites] N Engl J Med. 1997 Jul 24;337(4):223-9 [9227927.001]
  • [Cites] J Natl Cancer Inst. 1997 Nov 5;89(21):1616-20 [9362160.001]
  • [Cites] Lancet. 1998 Oct 3;352(9134):1087-92 [9798583.001]
  • [Cites] Blood. 2005 Feb 15;105(4):1652-9 [15459011.001]
  • [Cites] Cancer Cell. 2005 Feb;7(2):129-41 [15710326.001]
  • [Cites] Haematologica. 2005 Feb;90(2):232-7 [15710577.001]
  • [Cites] Cancer. 2005 Apr 15;103(8):1659-69 [15747376.001]
  • [Cites] Acta Haematol. 2005;113(3):155-62 [15870485.001]
  • [Cites] Cancer. 2005 May 15;103(10):2099-108 [15830345.001]
  • [Cites] Haematologica. 2005 Jul;90(7):979-81 [15996937.001]
  • [Cites] Leukemia. 2005 Sep;19(9):1613-20 [15990868.001]
  • [Cites] J Clin Oncol. 2005 Oct 20;23(30):7583-93 [16234522.001]
  • [Cites] Leukemia. 2006 Jun;20(6):1061-6 [16642048.001]
  • [Cites] N Engl J Med. 2006 Jun 15;354(24):2531-41 [16775234.001]
  • [Cites] N Engl J Med. 2006 Jun 15;354(24):2542-51 [16775235.001]
  • [Cites] Blood. 2006 Jul 1;108(1):28-37 [16522812.001]
  • [Cites] Blood. 2006 Sep 1;108(5):1478-84 [16627756.001]
  • [Cites] Blood. 2006 Sep 15;108(6):1809-20 [16709930.001]
  • [Cites] Leuk Res. 2006 Dec;30(12):1577-9 [16630657.001]
  • [Cites] N Engl J Med. 2006 Dec 7;355(23):2408-17 [17151364.001]
  • [Cites] Blood. 2007 Jan 1;109(1):58-60 [16973963.001]
  • [Cites] Nat Med. 2007 Jan;13(1):13-4; author reply 15-6 [17206117.001]
  • [Cites] Nat Med. 2007 Jan;13(1):13; author reply 15-6 [17206118.001]
  • [Cites] Nat Med. 2007 Jan;13(1):15; author reply 15-6 [17206121.001]
  • [Cites] Eur J Cancer. 2007 Apr;43(6):974-8 [17336514.001]
  • [Cites] Blood. 2007 Apr 15;109(8):3207-13 [17185463.001]
  • [Cites] Blood. 2007 Apr 15;109(8):3496-9 [17192396.001]
  • [Cites] Pharmacoeconomics. 2007;25(6):481-96 [17523753.001]
  • [Cites] Leuk Res. 2007 Jun;31(6):865-8 [17208297.001]
  • [Cites] Bone Marrow Transplant. 2007 Jul;40(1):83-4 [17450179.001]
  • [Cites] Blood. 2007 Aug 15;110(4):1233-7 [17449798.001]
  • [Cites] Blood. 2007 Oct 1;110(7):2309-15 [17496201.001]
  • [Cites] Blood. 2007 Oct 15;110(8):2828-37 [17626839.001]
  • [Cites] Blood. 2007 Nov 15;110(10):3540-6 [17715389.001]
  • [Cites] Blood. 2007 Dec 1;110(12):4064-72 [17761829.001]
  • [Cites] Blood. 2008 Feb 1;111(3):1039-43 [17932248.001]
  • [Cites] Cancer. 2008 Feb 15;112(4):837-45 [18085610.001]
  • [Cites] Blood. 2008 Feb 15;111(4):1834-9 [18048643.001]
  • [Cites] Blood. 2008 Feb 15;111(4):1774-80 [18055868.001]
  • [Cites] Leukemia. 2008 Jun;22(6):1200-6 [18401416.001]
  • [Cites] J Clin Oncol. 2008 Jul 1;26(19):3204-12 [18541900.001]
  • [Cites] J Clin Oncol. 2008 Jul 10;26(20):3358-63 [18519952.001]
  • [Cites] Blood. 2008 Dec 1;112(12):4437-44 [18716134.001]
  • [Cites] Haematologica. 2008 Dec;93(12):1792-6 [18838477.001]
  • [Cites] Leukemia. 2008 Dec;22(12):2176-83 [18754032.001]
  • [Cites] Haematologica. 2009 Feb;94(2):205-12 [19144656.001]
  • [Cites] Clin Lymphoma Myeloma. 2008 Mar;8 Suppl 3:S82-8 [19254885.001]
  • [Cites] Blood. 2009 Mar 5;113(10):2154-60 [19060245.001]
  • [Cites] Leukemia. 2009 Jun;23(6):1193-6 [19242496.001]
  • [Cites] Leukemia. 2009 Jun;23(6):1054-61 [19282833.001]
  • [Cites] Blood. 2009 Jun 18;113(25):6322-9 [19369231.001]
  • [Cites] J Clin Oncol. 2009 Jul 20;27(21):3472-9 [19487385.001]
  • [Cites] Blood. 2009 Sep 3;114(10):2037-43 [19567878.001]
  • [Cites] Cancer. 2009 Sep 15;115(18):4136-47 [19536906.001]
  • [Cites] Blood. 2009 Sep 24;114(13):2598-605 [19625707.001]
  • [Cites] J Natl Compr Canc Netw. 2009 Oct;7(9):984-1023 [19878641.001]
  • [Cites] J Clin Oncol. 2009 Dec 10;27(35):6041-51 [19884523.001]
  • [Cites] Nature. 1973 Jun 1;243(5405):290-3 [4126434.001]
  • (PMID = 20221270.001).
  • [ISSN] 1866-0452
  • [Journal-full-title] Deutsches Ärzteblatt international
  • [ISO-abbreviation] Dtsch Arztebl Int
  • [Language] eng
  • [Publication-type] Journal Article; Meta-Analysis; Review
  • [Publication-country] Germany
  • [Chemical-registry-number] 0 / Benzamides; 0 / Piperazines; 0 / Pyrimidines; 8A1O1M485B / Imatinib Mesylate
  • [Number-of-references] 98
  • [Other-IDs] NLM/ PMC2835925
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4. Schultheis B, Heissig B, Pasternak G, Hörner S, Hehlmann R: Interferon-alpha-treated patients with chronic myelogenous leukemia show BCR/ABL-positive peripheral blood progenitor cells surviving long-term culture. Folia Biol (Praha); 2000;46(6):251-5
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  • [Title] Interferon-alpha-treated patients with chronic myelogenous leukemia show BCR/ABL-positive peripheral blood progenitor cells surviving long-term culture.
  • Several groups have shown that Ph-progenitors reappear in LTC of CML bone marrow or PBMNC when the cell preparations were derived from newly diagnosed Ph-positive patients or after induction chemotherapy.
  • We have tested the hypothesis whether LTC may further decrease CML progenitors if the cells to be cultured were from IFN-treated patients.
  • In our experiments, PBMNC were cultured from 7 IFN- and 5 HU-treated patients in stable chronic phase of the disease, and from 9 patients at diagnosis.
  • Progenitor cells in PBMNC were quantitatively analyzed before and after 35 days of LTC by combining the clonogenic assay in semisolid medium with dual-color interphase FISH for identification of the BCR/ABL status of colony-forming progenitor cells.
  • A median of 22 colonies (range 7-88) before and 30 colonies (5-71) after LTC were analyzed per patient.
  • Our results show that the number of BCR/ABL-positive CFC before and after LTC was approximately the same.
  • This was independent of IFN or HU therapy.
  • In the IFN group there were 58% (median) BCR/ABL-positive CFC before and 54% (median) after LTC of PBMNC.
  • In the HU group, 80% of CFC were BCR/ABL-positive before and 85% after LTC.
  • A complete elimination of BCR/ABL-positive cells was not achieved.
  • We conclude that CML early progenitors in PBMNC of IFN-treated CML patients may survive LTC.
  • [MeSH-major] Biomarkers, Tumor / blood. Fusion Proteins, bcr-abl / blood. Immunologic Factors / therapeutic use. Interferon-alpha / therapeutic use. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy. Neoplastic Cells, Circulating
  • [MeSH-minor] Antineoplastic Agents, Alkylating / therapeutic use. Humans. Hydroxyurea / therapeutic use. In Situ Hybridization, Fluorescence. Leukemia, Myeloid, Chronic-Phase / blood. Leukemia, Myeloid, Chronic-Phase / drug therapy. Leukemia, Myeloid, Chronic-Phase / genetics. Leukemia, Myeloid, Chronic-Phase / pathology. Neoplasm, Residual. Tumor Cells, Cultured. Tumor Stem Cell Assay

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  • (PMID = 11140858.001).
  • [ISSN] 0015-5500
  • [Journal-full-title] Folia biologica
  • [ISO-abbreviation] Folia Biol. (Praha)
  • [Language] eng
  • [Publication-type] Comparative Study; Journal Article
  • [Publication-country] Czech Republic
  • [Chemical-registry-number] 0 / Antineoplastic Agents, Alkylating; 0 / Biomarkers, Tumor; 0 / Immunologic Factors; 0 / Interferon-alpha; EC 2.7.10.2 / Fusion Proteins, bcr-abl; X6Q56QN5QC / Hydroxyurea
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5. Moser AM, Manor E, Narkis G, Kapelushnik J: Imatinib resistant chronic myelogenous leukemia, BCR-ABL positive by chromosome and FISH analyses but negative by PCR, in a child progressing to acute basophilic leukemia: cytogenetic follow-up. Cancer Genet Cytogenet; 2006 Oct 1;170(1):54-7
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  • [Title] Imatinib resistant chronic myelogenous leukemia, BCR-ABL positive by chromosome and FISH analyses but negative by PCR, in a child progressing to acute basophilic leukemia: cytogenetic follow-up.
  • The case of an 11-year-old child with adult-type chronic myeloid leukemia, Philadelphia (BCR-ABL) positive, reverse transcription-polymerase chain reaction negative for the major, minor, and micro breakpoints is presented.
  • In the course of 3 years, the child failed to respond to treatment with hydroxyurea, refused all therapy for 6 months, was intolerant to alpha-interferon and progressed, while on imatinib, to acute basophilic leukemia.
  • A secondary cytogenetic clonal evolution, i(17q), developed during hydroxyurea treatment and a tertiary clonal evolution, +8, was detected during imatinib treatment.
  • It is not clear to what extent the several factors (undefined BCR-ABL breakpoint, treatment avoidance, and initial treatment choices, alone or in combination) played a role in the imatinib relapse and resistance and in the disease progression.
  • [MeSH-major] Antineoplastic Agents / therapeutic use. Genes, abl. Leukemia, Basophilic, Acute / surgery. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics. Piperazines / therapeutic use. Pyrimidines / therapeutic use
  • [MeSH-minor] Benzamides. Bone Marrow Transplantation. Child. Disease Progression. Drug Resistance, Neoplasm. Humans. Imatinib Mesylate. Immunophenotyping. In Situ Hybridization, Fluorescence. Male. Reverse Transcriptase Polymerase Chain Reaction

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  • (PMID = 16965955.001).
  • [ISSN] 0165-4608
  • [Journal-full-title] Cancer genetics and cytogenetics
  • [ISO-abbreviation] Cancer Genet. Cytogenet.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Benzamides; 0 / Piperazines; 0 / Pyrimidines; 8A1O1M485B / Imatinib Mesylate
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6. Topaly J, Zeller WJ, Fruehauf S: Synergistic activity of the new ABL-specific tyrosine kinase inhibitor STI571 and chemotherapeutic drugs on BCR-ABL-positive chronic myelogenous leukemia cells. Leukemia; 2001 Mar;15(3):342-7
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  • [Title] Synergistic activity of the new ABL-specific tyrosine kinase inhibitor STI571 and chemotherapeutic drugs on BCR-ABL-positive chronic myelogenous leukemia cells.
  • The ABL-specific tyrosine kinase inhibitor STI571 (formerly CGP57148B) induced cytogenetic remissions in 33% of chronic myelogenous leukemia (CML) patients in a phase I trial (Druker et al 1999).
  • Combination therapy may increase this proportion.
  • We tested whether combinations of STI571 and cytarabine or other chemotherapeutic agents such as hydroxyurea, mafosfamide or etoposide would display synergistic activity in BCR-ABL-positive chronic myelogenous leukemia (CML) cell lines derived from patients in blast crisis.
  • In addition, the toxicity of these combinations on BCR-ABL-negative cells was investigated.
  • The drug interactions were analyzed using the median-effect method of Chou and Talalay.
  • At growth inhibition levels of over 50%, STI571 + cytarabine as well as STI571 + etoposide were significantly synergistic (CI < 1, P < 0.05) in the BCR-ABL-positive cell lines evaluated.
  • At 60% inhibition or higher, a similar synergistic pattern became apparent for STI571 + mafosfamide (P < 0.05), while STI571 + hydroxyurea showed ambiguous, cell line-dependent synergism (BV173), additivity (EM-3) or antagonism (K562) in CML cell lines.
  • Furthermore, the BCR-ABL-negative HL-60, KG1a and normal CD34+ progenitor cells were not affected by 0.8 microM STI571, a concentration which produced more than 50% growth inhibition in all BCR-ABL-positive cells tested, and no potentiation of growth inhibition was observed in these BCR-ABL-negative cells when STI571 was combined with chemotherapeutic agents.
  • Our in vitro data with CML blast crisis cell lines strongly suggest that combinations of STI571 with cytarabine or etoposide be rapidly considered for clinical testing.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / pharmacology. Enzyme Inhibitors / pharmacology. Fusion Proteins, bcr-abl / metabolism. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology. Piperazines / pharmacology. Protein-Tyrosine Kinases / antagonists & inhibitors. Pyrimidines / pharmacology
  • [MeSH-minor] Benzamides. Cytarabine / administration & dosage. Dose-Response Relationship, Drug. Drug Synergism. Humans. Hydroxyurea / administration & dosage. Imatinib Mesylate. Remission Induction

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  • (PMID = 11237055.001).
  • [ISSN] 0887-6924
  • [Journal-full-title] Leukemia
  • [ISO-abbreviation] Leukemia
  • [Language] eng
  • [Publication-type] Clinical Trial; Clinical Trial, Phase I; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Benzamides; 0 / Enzyme Inhibitors; 0 / Piperazines; 0 / Pyrimidines; 04079A1RDZ / Cytarabine; 8A1O1M485B / Imatinib Mesylate; EC 2.7.10.1 / Protein-Tyrosine Kinases; EC 2.7.10.2 / Fusion Proteins, bcr-abl; X6Q56QN5QC / Hydroxyurea
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7. Beham-Schmid C, Apfelbeck U, Sill H, Tsybrovsky O, Höfler G, Haas OA, Linkesch W: Treatment of chronic myelogenous leukemia with the tyrosine kinase inhibitor STI571 results in marked regression of bone marrow fibrosis. Blood; 2002 Jan 1;99(1):381-3
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  • [Title] Treatment of chronic myelogenous leukemia with the tyrosine kinase inhibitor STI571 results in marked regression of bone marrow fibrosis.
  • Morphologic bone marrow changes in patients with BCR-ABL-positive chronic myelogenous leukemia (CML) were investigated during treatment with the tyrosine kinase inhibitor STI571.
  • Bone marrow trephine biopsy specimens from 23 pretreated patients with CML were examined morphologically and by morphometry before and 6 weeks and 3 months after the initiation of STI571 therapy (Glivec, Novartis, Basel, Switzerland).
  • Bone marrow changes during treatment showed a quantitative normalization of erythropoiesis, a marked reduction of granulopoiesis, and a significant decrease in megakaryocytes with the reappearance of normal-sized forms.
  • These results may expand the profile of STI571 and may offer novel therapeutic possibilities in diseases with bone marrow fibrosis.
  • [MeSH-major] Enzyme Inhibitors / therapeutic use. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology. Piperazines / therapeutic use. Primary Myelofibrosis / drug therapy. Protein-Tyrosine Kinases / antagonists & inhibitors. Pyrimidines / therapeutic use
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. Antineoplastic Agents / therapeutic use. Benzamides. Biopsy. Bone Marrow / pathology. Erythropoiesis. Female. Granulocytes / pathology. Hematopoiesis. Humans. Imatinib Mesylate. Male. Megakaryocytes / pathology. Middle Aged. Remission Induction

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  • (PMID = 11756197.001).
  • [ISSN] 0006-4971
  • [Journal-full-title] Blood
  • [ISO-abbreviation] Blood
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Benzamides; 0 / Enzyme Inhibitors; 0 / Piperazines; 0 / Pyrimidines; 8A1O1M485B / Imatinib Mesylate; EC 2.7.10.1 / Protein-Tyrosine Kinases
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8. Myojo T, Hino N: Complete remission from chronic myelogenous leukemia--blastic crisis caused by reduced intensity stem cell transplantation following partial remission due to imatinib. Intern Med; 2004 Feb;43(2):126-30
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  • [Title] Complete remission from chronic myelogenous leukemia--blastic crisis caused by reduced intensity stem cell transplantation following partial remission due to imatinib.
  • We report a 55-year-old man who showed no change after chemotherapy for chronic myelogenous leukemia-blastic crisis (CML-BC) in 1998.
  • Allo-peripheral blood stem cell transplantation (PBSCT) was then performed and Complete remission (CR) was achieved, but recurrence was seen in 2001.
  • The bcr-abl gene disappeared and Ph1 chromosome disappearance was ascertained.
  • CR was thus achieved.
  • There are still no established radical methods of treating CML-BC.
  • Thus, therapy by allograft after the patient has entered hematological remission with imatinib is considered a new way of dealing with cases of CML-BC.
  • [MeSH-major] Blast Crisis / drug therapy. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / surgery. Peripheral Blood Stem Cell Transplantation / methods. Piperazines / therapeutic use. Protein-Tyrosine Kinases / antagonists & inhibitors. Pyrimidines / therapeutic use
  • [MeSH-minor] Benzamides. Bone Marrow / pathology. Genes, abl. Humans. Hyperplasia. Imatinib Mesylate. Male. Middle Aged. Philadelphia Chromosome. Translocation, Genetic

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  • (PMID = 15005255.001).
  • [ISSN] 0918-2918
  • [Journal-full-title] Internal medicine (Tokyo, Japan)
  • [ISO-abbreviation] Intern. Med.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] Japan
  • [Chemical-registry-number] 0 / Benzamides; 0 / Piperazines; 0 / Pyrimidines; 8A1O1M485B / Imatinib Mesylate; EC 2.7.10.1 / Protein-Tyrosine Kinases
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9. Thiele J, Kvasnicka HM, Schmitt-Graeff A, Leder LD, Schaefer HE: Changing patterns of histological subgroups during therapy of Ph1+ chronic myelogenous leukaemia. Histopathology; 2000 Oct;37(4):355-62
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  • [Title] Changing patterns of histological subgroups during therapy of Ph1+ chronic myelogenous leukaemia.
  • AIMS: Bone marrow histopathology reveals a striking heterogeneity at diagnosis of Philadelphia chromosome positive (Ph1+) chronic myelogenous leukaemia (CML).
  • However, little information exists on whether these groups represent stable categories of the different classification systems and whether therapeutic regimes exert any influence on the putative shift of histological patterns.
  • There were at least two representative trephines taken at diagnosis and at median intervals of 16 months.
  • These consisted of a granulocytic (51 patients), a predominantly megakaryocytic (73 patients) and a myelofibrotic pattern (49 patients).
  • Follow-up biopsies revealed that a significant transition of histological groups occurred and that, independently of treatment modalities, the myelofibrotic category was associated with an unfavourable prognosis.
  • However, these patients showed no prevalence of either a pre-existing granulocytic or megakaryocytic growth.
  • Myelofibrotic changes were significantly associated with interferon (IFN) and busulfan (BU) therapy.
  • On the other hand, a transition of a myelofibrotic into a nonfibrotic subtype was detectable in 17 of the 49 patients under study and related to hydroxyurea (HU) treatment.
  • CONCLUSIONS: Histological classification systems of bone marrow features in CML do not represent stable patterns, but may be significantly altered by therapy, in particular IFN and HU.
  • [MeSH-major] Bone Marrow / pathology. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology
  • [MeSH-minor] Adult. Antineoplastic Agents / therapeutic use. Busulfan / therapeutic use. Granulocytes / drug effects. Granulocytes / pathology. Humans. Hydroxyurea / therapeutic use. Interferon-alpha / therapeutic use. Megakaryocytes / drug effects. Megakaryocytes / pathology. Primary Myelofibrosis / drug therapy. Primary Myelofibrosis / pathology. Recombinant Proteins. Retrospective Studies

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  • (PMID = 11012743.001).
  • [ISSN] 0309-0167
  • [Journal-full-title] Histopathology
  • [ISO-abbreviation] Histopathology
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] ENGLAND
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Interferon-alpha; 0 / Recombinant Proteins; 99210-65-8 / interferon alfa-2b; G1LN9045DK / Busulfan; X6Q56QN5QC / Hydroxyurea
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10. Ross JS, Schenkein DP, Pietrusko R, Rolfe M, Linette GP, Stec J, Stagliano NE, Ginsburg GS, Symmans WF, Pusztai L, Hortobagyi GN: Targeted therapies for cancer 2004. Am J Clin Pathol; 2004 Oct;122(4):598-609
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  • [Title] Targeted therapies for cancer 2004.
  • The regulatory agency approvals in the United States and Europe of imatinib mesylate (Gleevec) for patients with bcr/abl-positive chronic myelogenous leukemia, cetuximab (Erbitux) for patients with epidermal growth factor receptor overexpressing metastatic colorectal cancer, the antiangiogenesis agent bevacizumab (Avastin), and the proteasome inhibitor bortezomib (Velcade)--and the considerable public interest in new anticancer drugs that take advantage of specific genetic defects that render the malignant cells more likely to respond to specific treatment--are driving a new era of integrated diagnostics and therapeutics.
  • The recent discovery of a drug response predicting activating mutation in the epidermal growth factor receptor gene for patients with non-small cell lung cancer treated with gefitinib (Iressa) has intensified this interest.
  • In this review, the history of targeted anticancer therapies is highlighted, with focus on the development of molecular diagnostics for hematologic malignancies and the emergence of trastuzumab (Herceptin), an antibody-based targeted therapy for HER-2/neu overexpressing metastatic breast cancer: The potential of pharmacogenomic strategies and the use of high-density genomic microarrays to classify and select therapy for cancer are briefly considered.
  • This review also considers the widely held view that, in the next 5 to 10 years, the clinical application of molecular diagnostics will further revolutionize the drug discovery and development process; customize the selection, dosing, route of administration of existing and new therapeutic agents; and truly personalize medical care for cancer patients.
  • [MeSH-major] Neoplasms / therapy
  • [MeSH-minor] Aminoglycosides / therapeutic use. Antibodies, Monoclonal / therapeutic use. Antibodies, Monoclonal, Humanized. Antibodies, Monoclonal, Murine-Derived. Bevacizumab. Breast Neoplasms / drug therapy. Cetuximab. Erlotinib Hydrochloride. Humans. Pharmacogenetics. Quinazolines / therapeutic use. Rituximab. Trastuzumab

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  • (PMID = 15487459.001).
  • [ISSN] 0002-9173
  • [Journal-full-title] American journal of clinical pathology
  • [ISO-abbreviation] Am. J. Clin. Pathol.
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Aminoglycosides; 0 / Antibodies, Monoclonal; 0 / Antibodies, Monoclonal, Humanized; 0 / Antibodies, Monoclonal, Murine-Derived; 0 / Quinazolines; 0 / gemtuzumab; 0 / ibritumomab tiuxetan; 2S9ZZM9Q9V / Bevacizumab; 4F4X42SYQ6 / Rituximab; DA87705X9K / Erlotinib Hydrochloride; P188ANX8CK / Trastuzumab; PQX0D8J21J / Cetuximab; S65743JHBS / gefitinib
  • [Number-of-references] 132
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11. Merkerova M, Bruchova H, Brdicka R: Expression analysis of PCNA gene in chronic myelogenous leukemia--combined application of siRNA silencing and expression arrays. Leuk Res; 2007 May;31(5):661-72
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  • [Title] Expression analysis of PCNA gene in chronic myelogenous leukemia--combined application of siRNA silencing and expression arrays.
  • Imatinib metylase is the first choice treatment for BCR/ABL positive chronic myelogenous leukemia (CML).
  • However, as some CML patients develop resistance to imatinib therapy, there is a significant interest in development of alternative treatment strategies, such as identifying targets other than BCR/ABL that may participate in CML.
  • Previously, we demonstrated strong PCNA up-regulation in CML patients.
  • To further study its role in CML pathogenesis, we performed silencing of PCNA expression followed by array experiments.
  • [MeSH-major] Gene Expression Profiling. Gene Expression Regulation, Leukemic. Gene Silencing. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics. Oligonucleotide Array Sequence Analysis. Proliferating Cell Nuclear Antigen / genetics. RNA, Small Interfering / pharmacology
  • [MeSH-minor] Apoptosis. Benzamides. Biomarkers, Tumor / genetics. Cell Proliferation. Drug Resistance, Neoplasm. Fusion Proteins, bcr-abl / metabolism. Humans. Imatinib Mesylate. Piperazines / therapeutic use. Pyrimidines / therapeutic use. RNA, Messenger / genetics. RNA, Messenger / metabolism. RNA, Neoplasm / genetics. RNA, Neoplasm / metabolism. Reverse Transcriptase Polymerase Chain Reaction. Tumor Cells, Cultured


12. Berger U, Engelich G, Maywald O, Pfirrmann M, Hochhaus A, Reiter A, Metzgeroth G, Gnad U, Hasford J, Heinze B, Heimpel H, Hossfeld DK, Kolb HJ, Löffler H, Pralle H, Queisser W, Hehlmann R, German CML-Study Group: Chronic myeloid leukemia in the elderly: long-term results from randomized trials with interferon alpha. Leukemia; 2003 Sep;17(9):1820-6
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  • [Title] Chronic myeloid leukemia in the elderly: long-term results from randomized trials with interferon alpha.
  • Chronic myeloid leukemia (CML) in older patients has not been studied well.
  • To assess the long-term outcome of older patients with Philadelphia- and/or BCR-ABL-positive CML, 199 patients aged >/=60 years representing 23% of 856 patients enrolled in the German randomized CML-studies I (interferon alpha (IFN) vs hydroxyurea (HU) vs busulfan (BU) and II (IFN+HU vs HU alone) were analyzed after a median observation time of 7 years.
  • Whereas 5-year survival in chemotherapy-treated older patients was inferior to that in younger patients (33 vs 46%, P=0.006 for HU and 29 vs 38%, P=0.042 for Bu), no significant survival difference could be verified in IFN-treated patients (46 vs 53%, P=0.077).
  • Adverse effects of IFN were similar in both age groups, but IFN dosage to achieve treatment goals was lower in older patients.
  • We conclude that the course of CML is not different in the elderly.
  • [MeSH-major] Antineoplastic Agents / therapeutic use. Interferon-alpha / therapeutic use. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy. Protein-Tyrosine Kinases / metabolism
  • [MeSH-minor] Adolescent. Adult. Aged. Aged, 80 and over. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Busulfan / therapeutic use. Child. Female. Follow-Up Studies. Fusion Proteins, bcr-abl. Humans. Hydroxyurea / therapeutic use. Leukocyte Count. Male. Middle Aged. Prognosis. Randomized Controlled Trials as Topic. Risk. Survival Rate. Treatment Outcome

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  • (PMID = 12970782.001).
  • [ISSN] 0887-6924
  • [Journal-full-title] Leukemia
  • [ISO-abbreviation] Leukemia
  • [Language] eng
  • [Publication-type] Comparative Study; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Interferon-alpha; EC 2.7.10.1 / Protein-Tyrosine Kinases; EC 2.7.10.2 / Fusion Proteins, bcr-abl; G1LN9045DK / Busulfan; X6Q56QN5QC / Hydroxyurea
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13. Miyachi K, Ihara A, Hankins RW, Murai R, Maehiro S, Miyashita H: Efficacy of imatinib mesylate (STI571) treatment for a patient with rheumatoid arthritis developing chronic myelogenous leukemia. Clin Rheumatol; 2003 Oct;22(4-5):329-32
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  • [Title] Efficacy of imatinib mesylate (STI571) treatment for a patient with rheumatoid arthritis developing chronic myelogenous leukemia.
  • We report on an 80-year-old man with rheumatoid arthritis (RA) who presented with chronic myelogenous leukemia (CML).
  • Five years after the onset of RA, the CML diagnosis was made.
  • The patient was treated for CML with 300 mg of imatinib mesylate (STI; signal transduction inhibitor 571) for 8 weeks.
  • Laboratory tests showed that the C-reactive protein level, percentage of cells exhibiting the Philadelphia chromosome (Ph1), WBC count, and Lansbury index for RA all dropped respectively from 7.5 mg/dl to 1.0 mg/dl, 74.9% to 1%, 25, 100/microl to 9900/microl, and 51% to 14%.
  • Administration of imatinib mesylate is felt to be effective in treating not only CML but also RA in the active stage.
  • [MeSH-major] Antineoplastic Agents / administration & dosage. Arthritis, Rheumatoid / complications. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / complications. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy. Piperazines / administration & dosage. Pyrimidines / administration & dosage
  • [MeSH-minor] Aged. Aged, 80 and over. Benzamides. Dose-Response Relationship, Drug. Drug Administration Schedule. Follow-Up Studies. Humans. Imatinib Mesylate. Male. Pain Measurement / drug effects. Range of Motion, Articular / drug effects. Risk Assessment. Severity of Illness Index. Treatment Outcome


14. Neviani P, Santhanam R, Oaks JJ, Eiring AM, Notari M, Blaser BW, Liu S, Trotta R, Muthusamy N, Gambacorti-Passerini C, Druker BJ, Cortes J, Marcucci G, Chen CS, Verrills NM, Roy DC, Caligiuri MA, Bloomfield CD, Byrd JC, Perrotti D: FTY720, a new alternative for treating blast crisis chronic myelogenous leukemia and Philadelphia chromosome-positive acute lymphocytic leukemia. J Clin Invest; 2007 Sep;117(9):2408-21
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  • [Title] FTY720, a new alternative for treating blast crisis chronic myelogenous leukemia and Philadelphia chromosome-positive acute lymphocytic leukemia.
  • Blast crisis chronic myelogenous leukemia (CML-BC) and Philadelphia chromosome-positive (Ph1-positive) acute lymphocytic leukemia (ALL) are 2 fatal BCR/ABL-driven leukemias against which Abl kinase inhibitors fail to induce a long-term response.
  • We recently reported that functional loss of protein phosphatase 2A (PP2A) activity is important for CML blastic transformation.
  • We assessed the therapeutic potential of the PP2A activator FTY720 (2-amino-2-[2-(4-octylphenyl)ethyl]-1,3-propanediol hydrochloride), an immunomodulator in Phase III trials for patients with multiple sclerosis or undergoing organ transplantation, in CML-BC and Ph1 ALL patient cells and in in vitro and in vivo models of these BCR/ABL+ leukemias.
  • Our data indicate that FTY720 induces apoptosis and impairs clonogenicity of imatinib/dasatinib-sensitive and -resistant p210/p190(BCR/ABL) myeloid and lymphoid cell lines and CML-BC(CD34+) and Ph1 ALL(CD34+/CD19+) progenitors but not of normal CD34+ and CD34+/CD19+ bone marrow cells.
  • Furthermore, pharmacologic doses of FTY720 remarkably suppress in vivo p210/p190(BCR/ABL)-driven [including p210/p190(BCR/ABL)(T315I)] leukemogenesis without exerting any toxicity.
  • Altogether, these results highlight the therapeutic relevance of rescuing PP2A tumor suppressor activity in Ph1 leukemias and strongly support the introduction of the PP2A activator FTY720 in the treatment of CML-BC and Ph1 ALL patients.

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  • [Cites] Nat Genet. 2002 Jan;30(1):48-58 [11753385.001]
  • [Cites] Leuk Res. 2002 Mar;26(3):301-10 [11792420.001]
  • [Cites] Br J Pharmacol. 2004 Nov;143(5):581-9 [15466446.001]
  • [Cites] Nature. 1973 Jun 1;243(5405):290-3 [4126434.001]
  • [Cites] Science. 1990 Feb 16;247(4944):824-30 [2406902.001]
  • [Cites] Mol Cell Biol. 1991 Apr;11(4):1988-95 [1706474.001]
  • [Cites] Proc Natl Acad Sci U S A. 1991 May 1;88(9):3589-93 [1708885.001]
  • [Cites] J Biol Chem. 1991 Aug 5;266(22):14486-90 [1860857.001]
  • [Cites] Nature. 1991 Sep 12;353(6340):170-3 [1716348.001]
  • [Cites] Blood. 1992 Dec 15;80(12):2983-90 [1467514.001]
  • [Cites] J Biol Chem. 1993 Jul 25;268(21):15523-30 [8393446.001]
  • [Cites] Blood. 1993 Sep 15;82(6):1929-36 [8400243.001]
  • [Cites] Leukemia. 1994 Jan;8(1):186-9 [8289486.001]
  • [Cites] Transplant Proc. 1998 Aug;30(5):2210-3 [9723444.001]
  • [Cites] J Exp Med. 1999 May 3;189(9):1399-412 [10224280.001]
  • [Cites] J Biol Chem. 1999 Sep 24;274(39):27351-8 [10488065.001]
  • [Cites] Carcinogenesis. 2004 Dec;25(12):2397-405 [15297371.001]
  • [Cites] Yonsei Med J. 2004 Dec 31;45(6):991-7 [15627289.001]
  • [Cites] Clin Cancer Res. 2005 Jan 1;11(1):12-9 [15671523.001]
  • [Cites] J Biol Chem. 2005 Feb 18;280(7):6238-44 [15569672.001]
  • [Cites] N Engl J Med. 2006 Jun 15;354(24):2542-51 [16775235.001]
  • [Cites] Blood. 2006 Sep 1;108(5):1478-84 [16627756.001]
  • [Cites] Br J Haematol. 1997 Jan;96(1):111-6 [9012696.001]
  • [Cites] Cancer Res. 2002 Mar 1;62(5):1410-9 [11888913.001]
  • [Cites] J Am Soc Nephrol. 2002 Apr;13(4):1073-83 [11912269.001]
  • [Cites] J Biol Chem. 2002 Jun 14;277(24):21453-7 [11967257.001]
  • [Cites] Blood. 2002 Sep 15;100(6):1965-71 [12200353.001]
  • [Cites] J Clin Invest. 2003 Mar;111(5):659-69 [12618520.001]
  • [Cites] Br J Pharmacol. 2003 Apr;138(7):1303-12 [12711631.001]
  • [Cites] Biochim Biophys Acta. 2003 May 12;1640(2-3):97-104 [12729918.001]
  • [Cites] Blood. 2003 May 15;101(10):4122-30 [12531792.001]
  • [Cites] Blood. 1994 Apr 15;83(8):2038-44 [8161775.001]
  • [Cites] Leuk Res. 1995 Jun;19(6):389-96 [7596151.001]
  • [Cites] Blood. 1995 Dec 15;86(12):4603-11 [8541551.001]
  • [Cites] Nat Med. 1996 May;2(5):561-6 [8616716.001]
  • [Cites] J Biol Chem. 1996 May 10;271(19):11059-62 [8626647.001]
  • [Cites] Blood. 1996 Oct 1;88(7):2375-84 [8839828.001]
  • [Cites] Oncogene. 1997 Nov 6;15(19):2333-42 [9393877.001]
  • [Cites] J Urol. 2003 Jun;169(6):2372-7 [12771800.001]
  • [Cites] Leuk Res. 2003 Aug;27(8):709-17 [12801529.001]
  • [Cites] Cancer. 2003 Oct 1;98(7):1337-54 [14508819.001]
  • [Cites] Cancer Res. 2003 Sep 15;63(18):5962-9 [14522923.001]
  • [Cites] Oncogene. 2003 Oct 20;22(47):7389-95 [14576846.001]
  • [Cites] Transplant Proc. 2004 Mar;36(2 Suppl):531S-543S [15041402.001]
  • [Cites] J Clin Pharmacol. 2004 May;44(5):532-7 [15102874.001]
  • [Cites] J Org Chem. 2004 May 28;69(11):3950-2 [15153030.001]
  • [Cites] Blood. 2004 Jun 1;103(11):4010-22 [14982876.001]
  • [Cites] Prostaglandins Other Lipid Mediat. 2004 Jan;73(1-2):29-45 [15165029.001]
  • [Cites] Am J Transplant. 2004 Jul;4(7):1019-25 [15196057.001]
  • [Cites] Hematol Oncol Clin North Am. 2004 Jun;18(3):545-68, vii-viii [15271392.001]
  • [Cites] Nat Rev Cancer. 2004 Aug;4(8):604-16 [15286740.001]
  • [Cites] Proc Natl Acad Sci U S A. 2004 Oct 12;101(41):14788-93 [15466700.001]
  • [Cites] IDrugs. 2005 Mar;8(3):236-53 [15772896.001]
  • [Cites] Blood. 2005 Apr 1;105(7):2640-53 [15618470.001]
  • [Cites] Circ Res. 2005 Apr 29;96(8):913-20 [15802614.001]
  • [Cites] Cancer Res. 2005 Jun 1;65(11):4500-5 [15930265.001]
  • [Cites] Nat Med. 2005 Jun;11(6):630-7 [15908956.001]
  • [Cites] Clin Sci (Lond). 2005 Jul;109(1):13-25 [15966868.001]
  • [Cites] Mol Cell Biol. 2005 Aug;25(15):6464-74 [16024784.001]
  • [Cites] Cancer Res. 2005 Aug 15;65(16):7478-84 [16103102.001]
  • [Cites] J Immunol. 2005 Sep 1;175(5):2913-24 [16116177.001]
  • [Cites] Mol Cancer Ther. 2005 Sep;4(9):1430-8 [16170036.001]
  • [Cites] J Clin Pharmacol. 2005 Nov;45(11):1268-78 [16239360.001]
  • [Cites] Cancer Cell. 2005 Nov;8(5):355-68 [16286244.001]
  • [Cites] Pharmacol Ther. 2005 Dec;108(3):308-19 [15951022.001]
  • [Cites] Clin Cancer Res. 2005 Dec 1;11(23):8458-66 [16322309.001]
  • [Cites] Blood. 2006 Feb 15;107(4):1454-8 [16223773.001]
  • [Cites] NeuroRx. 2005 Oct;2(4):638-49 [16489371.001]
  • [Cites] Blood. 2006 Mar 15;107(6):2507-16 [16293596.001]
  • [Cites] N Engl J Med. 2006 Jun 15;354(24):2531-41 [16775234.001]
  • [Cites] Blood. 2000 Feb 1;95(3):1007-13 [10648416.001]
  • [Cites] Proc Natl Acad Sci U S A. 2000 Sep 26;97(20):10832-7 [10995457.001]
  • [Cites] Biochem Biophys Res Commun. 2001 Feb 23;281(2):282-8 [11181042.001]
  • [Cites] Biochem J. 2001 Feb 1;353(Pt 3):417-39 [11171037.001]
  • [Cites] Cell Signal. 2001 Jan;13(1):7-16 [11257442.001]
  • [Cites] N Engl J Med. 2001 Apr 5;344(14):1038-42 [11287973.001]
  • [Cites] J Interferon Cytokine Res. 2001 Jun;21(6):369-78 [11440634.001]
  • (PMID = 17717597.001).
  • [ISSN] 0021-9738
  • [Journal-full-title] The Journal of clinical investigation
  • [ISO-abbreviation] J. Clin. Invest.
  • [Language] ENG
  • [Grant] United States / NCI NIH HHS / CA / CA16058; United States / NCI NIH HHS / CA / CA101140; United States / NCI NIH HHS / CA / R01 CA095512; United States / NCI NIH HHS / CA / U10 CA101140; United States / NCI NIH HHS / CA / CA095512; United States / NCI NIH HHS / CA / P30 CA016058
  • [Publication-type] Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Benzamides; 0 / Piperazines; 0 / Propylene Glycols; 0 / Pyrimidines; 0 / Thiazoles; 8A1O1M485B / Imatinib Mesylate; EC 2.7.10.2 / Fusion Proteins, bcr-abl; EC 3.1.3.16 / Phosphoprotein Phosphatases; EC 3.1.3.16 / Protein Phosphatase 2; G926EC510T / Fingolimod Hydrochloride; NGZ37HRE42 / Sphingosine; RBZ1571X5H / Dasatinib
  • [Other-IDs] NLM/ PMC1950458
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15. Liu WM, Lawrence AJ, Joel SP: The importance of drug scheduling and recovery phases in determining drug activity. Improving etoposide efficacy in BCR-ABL-positive CML cells. Eur J Cancer; 2002 Apr;38(6):842-50
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  • [Title] The importance of drug scheduling and recovery phases in determining drug activity. Improving etoposide efficacy in BCR-ABL-positive CML cells.
  • We have investigated the effect of etoposide schedule on cell cycle distribution, apoptosis and p21(waf1) and cdk1(p34) status in two bcr-abl-positive chronic myeloid leukaemia (CML) cell lines (K562 and KU812) and two small cell lung cancer (SCLC) cell lines (H69 and GLC4).
  • During a continuous 5-day exposure, the SCLC cell lines showed a time and concentration-dependent loss of cell viability, with an initial block in the G2/M phase of the cell cycle followed by apoptosis.
  • In contrast, the two CML cell lines showed no significant apoptosis or loss of viability after a similar block in G2/M.
  • However, when K562 or KU812 cells were placed in drug-free medium following a 3-day drug exposure there was marked, concentration-dependent apoptosis (% apoptosis after release at 1 microM etoposide in K562, 10% at 24 h, 30% at 48 h).
  • Our data also show that p21(waf1) does not increase after etoposide treatment in either H69 or GLC4 (both with mutated-p53).
  • Although K562 and KU812 cells are null-p53, the arrest in G2/M during drug exposure was associated with increased p21(waf1) and a decrease in cdk1 (both P<0.001 compared with controls).
  • Upon release of these cells from drug-medium, p21(waf1) gradually returned to control levels, which was associated with an easing of the block at G2/M and an induction of apoptosis.
  • This study highlights the importance of cell cycle regulatory proteins in drug sensitivity and resistance, and suggests that in cells such as K562 and KU812, a pulsed schedule may be more active than a single prolonged exposure.
  • [MeSH-major] Etoposide / administration & dosage. Fusion Proteins, bcr-abl / metabolism. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy
  • [MeSH-minor] CDC2 Protein Kinase / metabolism. Cyclin-Dependent Kinase Inhibitor p21. Cyclins / metabolism. Dose-Response Relationship, Drug. Drug Administration Schedule. Flow Cytometry. G2 Phase. Humans. Immunoblotting. Tumor Cells, Cultured

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  • (PMID = 11937320.001).
  • [ISSN] 0959-8049
  • [Journal-full-title] European journal of cancer (Oxford, England : 1990)
  • [ISO-abbreviation] Eur. J. Cancer
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 0 / CDKN1A protein, human; 0 / Cyclin-Dependent Kinase Inhibitor p21; 0 / Cyclins; 6PLQ3CP4P3 / Etoposide; EC 2.7.10.2 / Fusion Proteins, bcr-abl; EC 2.7.11.22 / CDC2 Protein Kinase
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16. Mizutani S, Kuroda J, Shimizu D, Horiike S, Taniwaki M: Emergence of chronic myelogenous leukemia during treatment for essential thrombocythemia. Int J Hematol; 2010 Apr;91(3):516-21
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  • [Title] Emergence of chronic myelogenous leukemia during treatment for essential thrombocythemia.
  • A 72-year-old male patient was initially diagnosed with essential thrombocythemia (ET), a Philadelphia chromosome-negative (Ph1(-)) chronic myeloproliferative disorder (CMPD), and was treated with hydroxyurea (HU).
  • After 9 years of diagnosis of ET, his peripheral leukocytes gradually increased, while his platelet count showed a decrease.
  • Bone marrow analysis disclosed Ph-positive chronic myelogenous leukemia (CML) in the chronic phase.
  • Administration of imatinib mesylate (IM), a Bcr-Abl tyrosine kinase inhibitor (TKI), induced complete hematologic response in a month, but was discontinued after 4 months because of Grade 3 pleural effusion (PE).
  • The treatment was switched to nilotinib which successfully induced a complete cytogenetic response (CCyR) after 5 months of TKI therapy and resolved the PE.
  • Since then, the patient has been treated for 8 months with a combination of nilotinib and HU which has successfully controlled both CML and ET.
  • This report includes a review of the characteristics of 15 reported cases with co-occurrence of CML and Bcr-Abl-negative CMPDs, including ours.
  • Although rare, care needs to be taken since, despite the often similar clinical features of the two diseases, they require completely different treatments.
  • [MeSH-major] Hydroxyurea / therapeutic use. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / complications. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / diagnosis. Thrombocythemia, Essential / complications. Thrombocythemia, Essential / drug therapy
  • [MeSH-minor] Aged. Antineoplastic Agents / therapeutic use. Humans. Male

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  • [Cites] Eur J Haematol. 2003 Apr;70(4):240-1 [12656748.001]
  • [Cites] Leukemia. 2005 Jun;19(6):1095-6 [15789065.001]
  • [Cites] Leukemia. 2008 Jul;22(7):1454-5 [18288134.001]
  • [Cites] Isr Med Assoc J. 2007 Jul;9(7):562-3 [17710794.001]
  • [Cites] Arch Pathol Lab Med. 2007 Nov;131(11):1719-24 [17979493.001]
  • [Cites] Leuk Res. 2008 Oct;32(10):1608-10 [18448166.001]
  • [Cites] Int J Hematol. 2008 May;87(4):446-8 [18409076.001]
  • [Cites] Lancet Oncol. 2007 Jul;8(7):658-60 [17613428.001]
  • [Cites] Int J Hematol. 2008 Sep;88(2):243-5 [18626727.001]
  • [Cites] Cancer Genet Cytogenet. 2003 Sep;145(2):172-5 [12935931.001]
  • [Cites] Eur J Haematol. 2008 Jul;81(1):75-6 [18331600.001]
  • [Cites] N Engl J Med. 2005 Apr 28;352(17):1779-90 [15858187.001]
  • [Cites] Cancer Genet Cytogenet. 2006 May;167(1):74-7 [16682291.001]
  • [Cites] Blood. 2005 Feb 1;105(3):973-7 [15388582.001]
  • [Cites] Leuk Res. 2009 Aug;33(8):1133-6 [19250672.001]
  • [Cites] Int J Hematol. 2006 Jun;83(5):443-9 [16787877.001]
  • [Cites] Br J Haematol. 2005 Mar;128(5):734-6 [15725099.001]
  • [Cites] Blood. 2005 Apr 1;105(7):2664-70 [15585653.001]
  • [Cites] Eur J Haematol. 2002 Aug;69(2):108-11 [12366715.001]
  • (PMID = 20146031.001).
  • [ISSN] 1865-3774
  • [Journal-full-title] International journal of hematology
  • [ISO-abbreviation] Int. J. Hematol.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article; Research Support, Non-U.S. Gov't; Review
  • [Publication-country] Japan
  • [Chemical-registry-number] 0 / Antineoplastic Agents; X6Q56QN5QC / Hydroxyurea
  • [Number-of-references] 19
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17. Williams RT, Roussel MF, Sherr CJ: Arf gene loss enhances oncogenicity and limits imatinib response in mouse models of Bcr-Abl-induced acute lymphoblastic leukemia. Proc Natl Acad Sci U S A; 2006 Apr 25;103(17):6688-93
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  • [Title] Arf gene loss enhances oncogenicity and limits imatinib response in mouse models of Bcr-Abl-induced acute lymphoblastic leukemia.
  • Mouse bone marrow cells transduced with retroviral vectors encoding either of two oncogenic Bcr-Abl isoforms (p210(Bcr-Abl) and p185(Bcr-Abl)) induce B cell lympholeukemias when transplanted into lethally irradiated mice.
  • When mouse bone marrow cells expressing Bcr-Abl are placed in short-term cultures selectively designed to support the outgrowth of pre-B cells, only those lacking one or two Arf alleles can initiate lympholeukemias when inoculated into immunocompetent, syngeneic recipient mice.
  • Although the ABL kinase inhibitor imatinib mesylate (Gleevec) provides highly effective treatment for BCR-ABL-positive chronic myelogenous leukemia, it has proven far less efficacious in the treatment of BCR-ABL-positive acute lymphoblastic leukemias (ALLs), many of which sustain deletions of the INK4A-ARF (CDKN2A) tumor suppressor locus.
  • Mice receiving Arf-/- or Arf+/- p210(Bcr-Abl)-positive pre-B cells do not achieve remission when maintained on high doses of oral imatinib therapy and rapidly succumb to lympholeukemia.
  • Although cells expressing the Bcr-Abl kinase can proliferate in the absence of IL-7, they remain responsive to this cytokine, which can reduce their sensitivity to imatinib.
  • Treatment of Arf-/-, p210(Bcr-Abl)-positive pre-B cells with imatinib together with an inhibitor of JAK kinases abrogates this resistance, suggesting that this combination may prove beneficial in the treatment of BCR-ABL-positive acute lymphoblastic leukemia.

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  • [Cites] Genes Dev. 1999 Oct 15;13(20):2658-69 [10541552.001]
  • [Cites] Proc Natl Acad Sci U S A. 1987 Sep;84(18):6558-62 [3498165.001]
  • [Cites] Genes Dev. 1999 Oct 15;13(20):2678-90 [10541554.001]
  • [Cites] Proc Natl Acad Sci U S A. 2001 Aug 14;98(17):9654-9 [11481442.001]
  • [Cites] Blood. 2001 Nov 1;98(9):2808-16 [11675355.001]
  • [Cites] Cancer Res. 2002 Jan 15;62(2):535-41 [11809706.001]
  • [Cites] Proc Natl Acad Sci U S A. 2002 Mar 19;99(6):3848-53 [11891301.001]
  • [Cites] Cancer Cell. 2002 Aug;2(2):103-12 [12204530.001]
  • [Cites] Cancer Cell. 2002 Aug;2(2):117-25 [12204532.001]
  • [Cites] Leukemia. 2004 Apr;18(4):693-702 [15044926.001]
  • [Cites] Nat Genet. 2004 May;36(5):453-61 [15098032.001]
  • [Cites] Methods Enzymol. 1987;150:275-86 [3501518.001]
  • [Cites] Hybridoma. 1994 Feb;13(1):37-44 [8200657.001]
  • [Cites] Curr Biol. 1994 Jan 1;4(1):1-7 [7922305.001]
  • [Cites] Cell. 1997 Nov 28;91(5):649-59 [9393858.001]
  • [Cites] Genes Dev. 1998 Aug 1;12(15):2424-33 [9694806.001]
  • [Cites] Genes Dev. 1998 Aug 1;12(15):2434-42 [9694807.001]
  • [Cites] Nature. 1998 Sep 10;395(6698):125-6 [9744268.001]
  • [Cites] Proc Natl Acad Sci U S A. 1998 Oct 27;95(22):13194-9 [9789064.001]
  • [Cites] Nature. 1999 Jan 14;397(6715):164-8 [9923679.001]
  • [Cites] J Natl Cancer Inst. 1960 Jul;25:85-109 [14427847.001]
  • [Cites] Hybrid Hybridomics. 2004 Oct;23(5):293-300 [15672607.001]
  • [Cites] Blood. 2005 Apr 1;105(7):2640-53 [15618470.001]
  • [Cites] Leukemia. 2005 May;19(5):713-20 [15789066.001]
  • [Cites] J Clin Oncol. 2005 Sep 10;23(26):6306-15 [16155013.001]
  • [Cites] Hematology Am Soc Hematol Educ Program. 2005;:183-7 [16304378.001]
  • [Cites] Cell Cycle. 2005 Nov;4(11):1593-8 [16205118.001]
  • [Cites] Cell. 2004 Aug 20;118(4):409-18 [15315754.001]
  • [Cites] Nature. 1973 Jun 1;243(5405):290-3 [4126434.001]
  • [Cites] Nature. 1980 Feb 28;283(5750):826-31 [6244493.001]
  • [Cites] Cell. 1984 Jan;36(1):93-9 [6319012.001]
  • [Cites] Science. 1987 Jan 2;235(4784):85-8 [3541203.001]
  • [Cites] Nature. 1987 Feb 12-18;325(6105):635-7 [3027581.001]
  • [Cites] Genes Dev. 1999 Oct 15;13(20):2670-7 [10541553.001]
  • (PMID = 16618932.001).
  • [ISSN] 0027-8424
  • [Journal-full-title] Proceedings of the National Academy of Sciences of the United States of America
  • [ISO-abbreviation] Proc. Natl. Acad. Sci. U.S.A.
  • [Language] ENG
  • [Grant] United States / NCI NIH HHS / CA / T32 CA070089; United States / NCI NIH HHS / CA / P01 CA071907; United States / NCI NIH HHS / CA / T32-CA70089; United States / NCI NIH HHS / CA / CA-21765; United States / NCI NIH HHS / CA / P30 CA021765; United States / NCI NIH HHS / CA / CA-71907
  • [Publication-type] Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Benzamides; 0 / Cdkn2a protein, mouse; 0 / Cyclin-Dependent Kinase Inhibitor p16; 0 / Interleukin-7; 0 / Piperazines; 0 / Pyrimidines; 0 / Tumor Suppressor Protein p14ARF; 8A1O1M485B / Imatinib Mesylate
  • [Other-IDs] NLM/ PMC1440588
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18. Uno K, Inukai T, Kayagaki N, Goi K, Sato H, Nemoto A, Takahashi K, Kagami K, Yamaguchi N, Yagita H, Okumura K, Koyama-Okazaki T, Suzuki T, Sugita K, Nakazawa S: TNF-related apoptosis-inducing ligand (TRAIL) frequently induces apoptosis in Philadelphia chromosome-positive leukemia cells. Blood; 2003 May 1;101(9):3658-67
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  • [Title] TNF-related apoptosis-inducing ligand (TRAIL) frequently induces apoptosis in Philadelphia chromosome-positive leukemia cells.
  • Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and Fas ligand (FasL) have been implicated in antitumor immunity and therapy.
  • In the present study, we investigated the sensitivity of Philadelphia chromosome (Ph1)-positive leukemia cell lines to TRAIL- or FasL-induced cell death to explore the possible contribution of these molecules to immunotherapy against Ph1-positive leukemias.
  • TRAIL, but not FasL, effectively induced apoptotic cell death in most of 5 chronic myelogenous leukemia-derived and 7 acute leukemia-derived Ph1-positive cell lines.
  • Moreover, primary leukemia cells from Ph1-positive acute lymphoblastic leukemia patients were also sensitive to TRAIL, but not to FasL, depending on DR4/DR5 expression.
  • Fas-associated death domain protein (FADD) and caspase-8, components of death-inducing signaling complex (DISC), as well as FLIP (FLICE [Fas-associating protein with death domain-like interleukin-1-converting enzyme]/caspase-8 inhibitory protein), a negative regulator of caspase-8, were expressed ubiquitously in Ph1-positive leukemia cell lines irrespective of their differential sensitivities to TRAIL and FasL.
  • Notably, TRAIL could induce cell death in the Ph1-positive leukemia cell lines that were refractory to a BCR-ABL-specific tyrosine kinase inhibitor imatinib mesylate (STI571; Novartis Pharma, Basel, Switzerland).
  • These results suggested the potential utility of recombinant TRAIL as a novel therapeutic agent and the possible contribution of endogenously expressed TRAIL to immunotherapy against Ph1-positive leukemias.
  • [MeSH-major] Apoptosis / drug effects. Arabidopsis Proteins. Intracellular Signaling Peptides and Proteins. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology. Membrane Glycoproteins / pharmacology. Neoplastic Stem Cells / drug effects. Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology. Tumor Necrosis Factor-alpha / pharmacology
  • [MeSH-minor] Amino Acid Chloromethyl Ketones / pharmacology. Apoptosis Regulatory Proteins. Benzamides. CASP8 and FADD-Like Apoptosis Regulating Protein. Carrier Proteins / physiology. Caspase 1 / physiology. Death Domain Receptor Signaling Adaptor Proteins. Drug Resistance, Neoplasm. Drug Screening Assays, Antitumor. Enzyme Inhibitors / pharmacology. Fas Ligand Protein. Fatty Acid Desaturases / physiology. Fusion Proteins, bcr-abl / antagonists & inhibitors. Humans. Imatinib Mesylate. Leupeptins / pharmacology. NF-kappa B / antagonists & inhibitors. Neoplasm Proteins / antagonists & inhibitors. Neoplasm Proteins / physiology. Peptides / pharmacology. Piperazines / pharmacology. Pyrimidines / pharmacology. Receptors, TNF-Related Apoptosis-Inducing Ligand. Receptors, Tumor Necrosis Factor / physiology. Recombinant Proteins / pharmacology. TNF-Related Apoptosis-Inducing Ligand. Tumor Cells, Cultured / drug effects. Tumor Cells, Cultured / pathology

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  • (PMID = 12506034.001).
  • [ISSN] 0006-4971
  • [Journal-full-title] Blood
  • [ISO-abbreviation] Blood
  • [Language] eng
  • [Publication-type] Comparative Study; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Amino Acid Chloromethyl Ketones; 0 / Apoptosis Regulatory Proteins; 0 / Arabidopsis Proteins; 0 / Benzamides; 0 / CASP8 and FADD-Like Apoptosis Regulating Protein; 0 / CFLAR protein, human; 0 / Carrier Proteins; 0 / Death Domain Receptor Signaling Adaptor Proteins; 0 / Enzyme Inhibitors; 0 / FASLG protein, human; 0 / Fas Ligand Protein; 0 / Intracellular Signaling Peptides and Proteins; 0 / Leupeptins; 0 / Membrane Glycoproteins; 0 / NF-kappa B; 0 / Neoplasm Proteins; 0 / Peptides; 0 / Piperazines; 0 / Pyrimidines; 0 / Receptors, TNF-Related Apoptosis-Inducing Ligand; 0 / Receptors, Tumor Necrosis Factor; 0 / Recombinant Proteins; 0 / SN50 peptide; 0 / TNF-Related Apoptosis-Inducing Ligand; 0 / TNFRSF10A protein, human; 0 / TNFRSF10B protein, human; 0 / TNFSF10 protein, human; 0 / Tumor Necrosis Factor-alpha; 0 / benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; 110044-82-1 / acetylleucyl-leucyl-norleucinal; 8A1O1M485B / Imatinib Mesylate; EC 1.14.19.- / Fatty Acid Desaturases; EC 1.14.99.- / Fad7 protein, Arabidopsis; EC 2.7.10.2 / Fusion Proteins, bcr-abl; EC 3.4.22.36 / Caspase 1
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19. Sick C, Schultheis B, Pasternak G, Kottke I, Hörner S, Heissig B, Hehlmann R: Predominantly BCR-ABL negative myeloid precursors in interferon-alpha treated chronic myelogenous leukemia: a follow-up study of peripheral blood colony-forming cells with fluorescence in situ hybridization. Ann Hematol; 2001 Jan;80(1):9-16
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  • [Title] Predominantly BCR-ABL negative myeloid precursors in interferon-alpha treated chronic myelogenous leukemia: a follow-up study of peripheral blood colony-forming cells with fluorescence in situ hybridization.
  • The mechanism and target cell of the life-prolonging effect of interferon-alpha (IFN-alpha) in chronic myelogenous leukemia (CML) are controversial.
  • We studied the influence of IFN-alpha treatment on the frequency of malignant hematopoietic precursor cells in the peripheral blood (PB) of CML patients during the course of the disease.
  • PB 10-day colony-forming cells (PB-CFCs) were assessed with regard to their quantity, lineage distribution, and BCR-ABL status, as determined by fluorescence in situ hybridization (FISH).
  • PB-CFC numbers were determined in 39 patients (29 in the chronic phase, 6 in an advanced stage, and 4 with progression to an advanced stage during follow-up).
  • Thirty-one patients were evaluated either once or several times to determine the BCR-ABL status of the colonies.
  • BCR-ABL negative PB-CFCs were detectable at diagnosis in 5 of 11 patients.
  • A major reduction of BCR-ABL positive colonies to <25% of PB-CFCs was observed in 10/13 determinable IFN-alpha treated patients in early and late chronic phases, indicating a high proportion of BCR-ABL negativity at the clonogenic cell level.
  • In contrast, only 3 of these patients had a cytogenetic response of <25% Philadelphia chromosome (Ph1)-positive metaphases in bone marrow cytogenetics.
  • Treatment with IFN-alpha and/or hydroxyurea (HU) during chronic phase was accompanied by a reduction of PB-CFCs to subnormal levels (median 24 CFCs/ml) compared to controls (median 207 CFCs/ml), untreated patients in chronic phase (median 25,979 CFCs/ml), and patients with advanced disease (median 6,047 CFCs/ml).
  • In blast crisis (6 patients), all colonies tested were BCR-ABL positive.
  • Our results show that IFN-alpha treatment leads to a marked reduction of malignant myeloid precursor cells in the PB of CML patients, which exceeds the degree of cytogenetic remission.
  • This offers an explanation for the good therapeutic efficacy and even life-prolonging effect of IFN-alpha, which is also observed in cytogenetic non-responders.
  • [MeSH-major] Fusion Proteins, bcr-abl / blood. Interferon-alpha / therapeutic use. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy
  • [MeSH-minor] Hematopoietic Stem Cells / drug effects. Humans. In Situ Hybridization, Fluorescence. Longitudinal Studies

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  • (PMID = 11233781.001).
  • [ISSN] 0939-5555
  • [Journal-full-title] Annals of hematology
  • [ISO-abbreviation] Ann. Hematol.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] Germany
  • [Chemical-registry-number] 0 / Interferon-alpha; EC 2.7.10.2 / Fusion Proteins, bcr-abl
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20. Chen ZC, You Y, Zhu XM, Li QB, Li WM, Zou P: [A clinical study of treating 120 cases of adult chronic myelocytic leukemia with imatinib mesylate]. Zhonghua Nei Ke Za Zhi; 2007 Dec;46(12):1003-6
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  • [Title] [A clinical study of treating 120 cases of adult chronic myelocytic leukemia with imatinib mesylate].
  • OBJECTIVE: To analyze and evaluate the clinical efficacy and safety of imatinib mesylate (IM) as a tyrosine kinase inhibitor on Ph-positive or BCR/ABL positive chronic myelogenous leukemia (CML).
  • METHODS: 120 patients diagnosed as CML with positive Ph chromosome were treated with IM 400 mg/d for CML in chronic phase (CP) (n = 90) or 600 mg/d for CML in accelerated or blastic phase (AP or BP) (n = 30) once daily.
  • Hematological, cytogenetic and molecular effects of IM on the disease process of these patients were evaluated with blood and marrow cells morphology examination, G-band conventional cytogenetics analysis for Ph chromosome and PCR assay for BCR/ABL gene.
  • The treatment efficacy and safety were retrospectively studied. RESULTS:.
  • (1) In CML-CP patients, after a follow-up of 9 ( range 3-42) months, cumulative complete hematological response (CHR), complete cytogenetic response (CCyR) and complete molecular response (CMR) rates were 73.3%, 66.7% and 54.4%, which was not influenced by prior treatment of interferon.
  • CMR was better when time from diagnosis to treatment with IM was < or = 6 months (P < 0.05).
  • It is significant that the time to first CHR and time to first CCyR were related with the time to first CCyR and the time to first negative BCR/ ABL, respectively (both P < 0.05), while there was no relation between the time to first CHR and the time to first negative BCR/ABL (P > 0.05). (2) CHR, CCyR and CMR rates of the patients with progressive course (AP and BP) were 43.3%, 25.9% and 25.0%, respectively.
  • The total mortality rate was 30.0%. (3) The mortality rate of the patients with age < or = 25 was higher than those >25 (P < 0.05). (4) Grade 3 leukocytopenia occurred in 16.0% of the patients and grade 3 thrombocytopenia in 18.0% of the patients and they 12 (5-20) weeks and 9 (3-16) weeks after the treatment, respectively.
  • CONCLUSION: IM can lead to considerable hematological, cytogenetic and molecular response rates in CML, especially CML-CP patients, with minor tolerable side effects.
  • [MeSH-major] Leukemia, Myeloid, Chronic-Phase / drug therapy. Piperazines / therapeutic use. Pyrimidines / therapeutic use
  • [MeSH-minor] Adolescent. Adult. Antineoplastic Agents / adverse effects. Antineoplastic Agents / therapeutic use. Benzamides. Female. Fusion Proteins, bcr-abl / genetics. Humans. Imatinib Mesylate. Male. Middle Aged. Philadelphia Chromosome. Retrospective Studies. Treatment Outcome

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  • (PMID = 18478917.001).
  • [ISSN] 0578-1426
  • [Journal-full-title] Zhonghua nei ke za zhi
  • [ISO-abbreviation] Zhonghua Nei Ke Za Zhi
  • [Language] chi
  • [Publication-type] English Abstract; Journal Article
  • [Publication-country] China
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Benzamides; 0 / Piperazines; 0 / Pyrimidines; 8A1O1M485B / Imatinib Mesylate; EC 2.7.10.2 / Fusion Proteins, bcr-abl
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21. Mahon FX, Hayette S, Lagarde V, Belloc F, Turcq B, Nicolini F, Belanger C, Manley PW, Leroy C, Etienne G, Roche S, Pasquet JM: Evidence that resistance to nilotinib may be due to BCR-ABL, Pgp, or Src kinase overexpression. Cancer Res; 2008 Dec 1;68(23):9809-16
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  • [Title] Evidence that resistance to nilotinib may be due to BCR-ABL, Pgp, or Src kinase overexpression.
  • Targeting the tyrosine kinase activity of Bcr-Abl is an attractive therapeutic strategy in chronic myeloid leukemia (CML) and in Bcr-Abl-positive acute lymphoblastic leukemia.
  • Whereas imatinib, a selective inhibitor of Bcr-Abl tyrosine kinase, is now used in frontline therapy for CML, second-generation inhibitors of Bcr-Abl tyrosine kinase such as nilotinib or dasatinib have been developed for the treatment of imatinib-resistant or imatinib-intolerant disease.
  • Overexpression of BCR-ABL and multidrug resistance gene (MDR-1) were found among the investigated mechanisms.
  • Moreover, failure of nilotinib treatment was accompanied by an increase of Lyn mRNA expression in patients with resistant CML.
  • Two Src kinase inhibitors (PP1 and PP2) partially removed resistance but did not significantly inhibit Bcr-Abl tyrosine kinase activity.
  • In contrast, dasatinib, a dual Bcr-Abl and Src kinase inhibitor, inhibited the phosphorylation of both BCR-ABL and Lyn, and induced apoptosis of the Bcr-Abl cell line overexpressing p53/56 Lyn.
  • [MeSH-major] Fusion Proteins, bcr-abl / biosynthesis. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / metabolism. P-Glycoprotein / biosynthesis. Pyrimidines / pharmacology. src-Family Kinases / biosynthesis
  • [MeSH-minor] Antineoplastic Agents. Dasatinib. Drug Resistance, Neoplasm. Humans. K562 Cells. RNA, Messenger / biosynthesis. RNA, Messenger / genetics. RNA, Small Interfering / genetics. Thiazoles / pharmacology. Transfection


22. Thiele J, Kvasnicka HM, Schmitt-Graeff A, Cvetanovska G, Blum N, Schaefer HE: Therapy-related changes of CD20+ and CD45RO+ lymphocyte subsets in chronic myeloid leukemia (CML): an immunohistochemical and morphometric study on sequential trephine biopsies of the bone marrow. Mod Pathol; 2000 Aug;13(8):888-96
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  • [Title] Therapy-related changes of CD20+ and CD45RO+ lymphocyte subsets in chronic myeloid leukemia (CML): an immunohistochemical and morphometric study on sequential trephine biopsies of the bone marrow.
  • Little information exists about the amount of CD45RO+-T- and CD20+-B-lymphocytes in the bone marrow of patients with Philadelphia chromosome-positive chronic myelogenous leukemia (Ph1+-CML) at presentation or regarding corresponding changes during therapy.
  • Therefore, an immunohistological and morphometric study was performed on 219 representative trephine biopsies of the bone marrow derived from 70 patients with repeated examinations during the course of Ph1+-CML.
  • In comparison to a control group and calculated per hematopoietic cells, the CML bone marrow showed about a 50% decrease in the total amount of lymphocytes.
  • Determination of CD45RO+ and CD20+ subsets revealed a significant enhancement during treatment.
  • Because of the different intervals (range, 10 to 25 mo) between first and last biopsy in the various therapeutic groups, results had to be modified by considering dynamic features.
  • This calculation included changes of the lymphocyte subpopulations related to time.
  • Contrasting the CD45RO+ lymphocytes, a relevant increase in the CD20+ subset could be observed after interferon-a treatment or corresponding combination regimens.
  • No significant correlations were found between fiber density at onset (first biopsy) or development of fibrosis and lymphocyte proliferations in the course of CML.
  • Our results are in keeping with the finding that a proper immune response consistent with an increased lymphocyte growth seems to be associated with a regression of the clonally-transformed cell population.
  • [MeSH-major] Antigens, CD20 / immunology. Antigens, CD45 / immunology. Antineoplastic Agents / therapeutic use. Bone Marrow / immunology. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy. Lymphocyte Subsets / immunology
  • [MeSH-minor] Adult. Biopsy. Busulfan / therapeutic use. Cohort Studies. Drug Therapy, Combination. Female. Humans. Hydroxyurea / therapeutic use. Immunoenzyme Techniques. Interferon-alpha / therapeutic use. Male. Middle Aged. Vincristine / therapeutic use

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  • (PMID = 10955456.001).
  • [ISSN] 0893-3952
  • [Journal-full-title] Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc
  • [ISO-abbreviation] Mod. Pathol.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] UNITED STATES
  • [Chemical-registry-number] 0 / Antigens, CD20; 0 / Antineoplastic Agents; 0 / Interferon-alpha; 5J49Q6B70F / Vincristine; EC 3.1.3.48 / Antigens, CD45; G1LN9045DK / Busulfan; X6Q56QN5QC / Hydroxyurea
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23. Jagani Z, Song K, Kutok JL, Dewar MR, Melet A, Santos T, Grassian A, Ghaffari S, Wu C, Yeckes-Rodin H, Ren R, Miller K, Khosravi-Far R: Proteasome inhibition causes regression of leukemia and abrogates BCR-ABL-induced evasion of apoptosis in part through regulation of forkhead tumor suppressors. Cancer Res; 2009 Aug 15;69(16):6546-55
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  • [Title] Proteasome inhibition causes regression of leukemia and abrogates BCR-ABL-induced evasion of apoptosis in part through regulation of forkhead tumor suppressors.
  • BCR-ABL plays an essential role in the pathogenesis of chronic myeloid leukemia (CML) and some cases of acute lymphocytic leukemia (ALL).
  • Although ABL kinase inhibitors have shown great promise in the treatment of CML, the persistence of residual disease and the occurrence of resistance have prompted investigations into the molecular effectors of BCR-ABL.
  • Here, we show that BCR-ABL stimulates the proteasome-dependent degradation of members of the forkhead family of tumor suppressors in vitro, in an in vivo animal model, and in samples from patients with BCR-ABL-positive CML or ALL.
  • As several downstream mediators of BCR-ABL are regulated by the proteasome degradation pathway, we also show that inhibition of this pathway, using bortezomib, causes regression of CML-like disease.
  • Bortezomib treatment led to inhibition of BCR-ABL-induced suppression of FoxO proteins and their proapoptotic targets, tumor necrosis factor-related apoptosis-inducing ligand and BIM, thereby providing novel insights into the molecular effects of proteasome inhibitor therapy.
  • We additionally show sensitivity of imatinib-resistant BCR-ABL T315I cells to bortezomib.
  • Our data delineate the involvement of FoxO proteins in BCR-ABL-induced evasion of apoptosis and provide evidence that bortezomib is a candidate therapeutic in the treatment of BCR-ABL-induced leukemia.

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  • [Cites] EMBO J. 1997 Oct 15;16(20):6151-61 [9321394.001]
  • [Cites] Blood. 1995 Jul 15;86(2):726-36 [7606002.001]
  • [Cites] Blood. 1998 Nov 15;92(10):3829-40 [9808576.001]
  • [Cites] Cell. 1999 Mar 19;96(6):857-68 [10102273.001]
  • [Cites] Proc Natl Acad Sci U S A. 1999 Jun 22;96(13):7421-6 [10377430.001]
  • [Cites] Haematologica. 2004 Dec;89(12):1428-33 [15590391.001]
  • [Cites] J Clin Oncol. 2005 Jan 20;23(3):630-9 [15659509.001]
  • [Cites] Cancer Cell. 2005 Feb;7(2):129-41 [15710326.001]
  • [Cites] Nat Rev Cancer. 2005 Mar;5(3):172-83 [15719031.001]
  • [Cites] Cancer Cell. 2005 Mar;7(3):227-38 [15766661.001]
  • [Cites] Oncogene. 2005 Mar 31;24(14):2317-29 [15688014.001]
  • [Cites] Mol Cancer Ther. 2005 Apr;4(4):686-92 [15827343.001]
  • [Cites] Blood. 2005 May 15;105(10):4021-7 [15665113.001]
  • [Cites] J Immunol. 2006 Apr 15;176(8):4757-65 [16585569.001]
  • [Cites] J Immunol. 2006 May 15;176(10):6302-12 [16670342.001]
  • [Cites] Blood. 2006 May 15;107(10):4063-70 [16424391.001]
  • [Cites] Cancer Res. 2006 Jun 15;66(12):6304-11 [16778207.001]
  • [Cites] Cell. 2007 Jan 26;128(2):309-23 [17254969.001]
  • [Cites] Cell. 2007 Jan 26;128(2):325-39 [17254970.001]
  • [Cites] Nat Rev Cancer. 2007 May;7(5):345-56 [17457302.001]
  • [Cites] Nat Rev Mol Cell Biol. 2007 Jun;8(6):440-50 [17522590.001]
  • [Cites] Blood. 2007 Jul 1;110(1):345-53 [17374740.001]
  • [Cites] Curr Oncol Rep. 2007 Sep;9(5):391-8 [17706168.001]
  • [Cites] Oncology (Williston Park). 2007 Jun;21(7):785-92; discussion 798-800 [17722741.001]
  • [Cites] J Clin Invest. 2007 Sep;117(9):2562-9 [17710227.001]
  • [Cites] Acta Physiol (Oxf). 2008 Jan;192(1):19-28 [18171426.001]
  • [Cites] Expert Opin Investig Drugs. 2008 Jun;17(6):865-78 [18491988.001]
  • [Cites] Blood. 1997 Dec 15;90(12):4947-52 [9389713.001]
  • [Cites] Mol Cell Biol. 2000 Feb;20(4):1179-86 [10648603.001]
  • [Cites] Curr Biol. 2000 Oct 5;10(19):1201-4 [11050388.001]
  • [Cites] Blood. 2000 Nov 15;96(10):3343-56 [11071626.001]
  • [Cites] N Engl J Med. 2001 Apr 5;344(14):1031-7 [11287972.001]
  • [Cites] Curr Oncol Rep. 2001 May;3(3):228-37 [11296133.001]
  • [Cites] Science. 2001 Aug 3;293(5531):876-80 [11423618.001]
  • [Cites] Blood. 2001 Nov 15;98(10):2948-57 [11698276.001]
  • [Cites] Semin Oncol. 2001 Dec;28(6):613-9 [11740819.001]
  • [Cites] Trends Mol Med. 2002;8(4 Suppl):S49-54 [11927288.001]
  • [Cites] Cancer Cell. 2002 Aug;2(2):117-25 [12204532.001]
  • [Cites] J Biol Chem. 2002 Dec 6;277(49):47928-37 [12351634.001]
  • [Cites] J Biol Chem. 2003 Apr 4;278(14):12361-6 [12517744.001]
  • [Cites] Proc Natl Acad Sci U S A. 2003 May 27;100(11):6523-8 [12750477.001]
  • [Cites] J Cell Biol. 2003 Aug 18;162(4):613-22 [12913110.001]
  • [Cites] J Biol Chem. 2003 Sep 19;278(38):35959-67 [12857750.001]
  • [Cites] Leuk Res. 2004 May;28 Suppl 1:S21-8 [15036938.001]
  • [Cites] Cell. 2004 Apr 16;117(2):225-37 [15084260.001]
  • [Cites] Oncogene. 2004 Apr 22;23(19):3338-49 [14981546.001]
  • [Cites] Blood. 2004 Jun 15;103(12):4622-9 [14962911.001]
  • [Cites] Science. 2004 Jul 16;305(5682):399-401 [15256671.001]
  • [Cites] Science. 1990 Feb 16;247(4944):824-30 [2406902.001]
  • [Cites] Mol Cell Biol. 1991 Feb;11(2):1107-13 [1846663.001]
  • [ErratumIn] Cancer Res. 2009 Sep 1;69(17):7130. Rodin, Heather Yeckes [corrected to Yeckes-Rodin, Heather]
  • (PMID = 19654305.001).
  • [ISSN] 1538-7445
  • [Journal-full-title] Cancer research
  • [ISO-abbreviation] Cancer Res.
  • [Language] ENG
  • [Grant] United States / NHLBI NIH HHS / HL / HL080192-05; United States / NHLBI NIH HHS / HL / HL080192; United States / NHLBI NIH HHS / HL / R01 HL080192; United States / NCI NIH HHS / CA / R01 CA131664; United States / NHLBI NIH HHS / HL / R01 HL080192-05; United States / NCI NIH HHS / CA / P30CA6516; United States / NCI NIH HHS / CA / R01 CA105306-05; United States / NCI NIH HHS / CA / R01 CA105306; United States / NCI NIH HHS / CA / CA105306; United States / NCI NIH HHS / CA / P30 CA006516; United States / NCI NIH HHS / CA / CA105306-05; United States / NCI NIH HHS / CA / CA131664
  • [Publication-type] Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Benzamides; 0 / Boronic Acids; 0 / Cysteine Proteinase Inhibitors; 0 / Forkhead Transcription Factors; 0 / Piperazines; 0 / Proteasome Inhibitors; 0 / Pyrazines; 0 / Pyrimidines; 0 / Tumor Suppressor Proteins; 69G8BD63PP / Bortezomib; 8A1O1M485B / Imatinib Mesylate; EC 2.7.10.2 / Fusion Proteins, bcr-abl
  • [Other-IDs] NLM/ NIHMS123965; NLM/ PMC2763358
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24. Greene LM, Kelly L, Onnis V, Campiani G, Lawler M, Williams DC, Zisterer DM: STI-571 (imatinib mesylate) enhances the apoptotic efficacy of pyrrolo-1,5-benzoxazepine-6, a novel microtubule-targeting agent, in both STI-571-sensitive and -resistant Bcr-Abl-positive human chronic myeloid leukemia cells. J Pharmacol Exp Ther; 2007 Apr;321(1):288-97
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  • [Title] STI-571 (imatinib mesylate) enhances the apoptotic efficacy of pyrrolo-1,5-benzoxazepine-6, a novel microtubule-targeting agent, in both STI-571-sensitive and -resistant Bcr-Abl-positive human chronic myeloid leukemia cells.
  • Interactions between the Bcr-Abl kinase inhibitor STI-571 (imatinib mesylate) and a novel microtubule-targeting agent (MTA), pyrrolo-1,5-benzoxazepine (PBOX)-6, were investigated in STI-571-sensitive and -resistant human chronic myeloid leukemia (CML) cells.
  • Cotreatment of PBOX-6 with STI-571 induced significantly more apoptosis in Bcr-Abl-positive CML cell lines (K562 and LAMA-84) than either drug alone (P < 0.01).
  • Cell cycle analysis of propidium iodide-stained cells showed that STI-571 significantly reduced PBOX-6-induced G2M arrest and polyploid formation with a concomitant increase in apoptosis.
  • Similar results were obtained in K562 CML cells using lead MTAs (paclitaxel and nocodazole) in combination with STI-571.
  • Potentiation of PBOX-6-induced apoptosis by STI-571 was specific to Bcr-Abl-positive leukemia cells with no cytoxic effects observed on normal peripheral blood cells.
  • The combined treatment of STI-571 and PBOX-6 was associated with the down-regulation of Bcr-Abl and repression of proteins involved in Bcr-Abl transformation, namely the antiapoptotic proteins Bcl-x(L) and Mcl-1.
  • Together, these findings highlight the potential clinical benefits in simultaneously targeting the microtubules and the Bcr-Abl oncoprotein in STI-571-sensitive and -resistant CML cells.
  • [MeSH-major] Apoptosis / drug effects. Fusion Proteins, bcr-abl / metabolism. Leukemia, Myeloid / drug therapy. Microtubules / drug effects. Oxazepines / pharmacology. Piperazines / pharmacology. Pyrimidines / pharmacology. Pyrroles / pharmacology
  • [MeSH-minor] Benzamides. Blotting, Western. Cell Cycle / drug effects. Cell Line, Tumor. Cell Survival / drug effects. Down-Regulation / physiology. Drug Resistance, Neoplasm. Drug Synergism. HL-60 Cells. Humans. Imatinib Mesylate. K562 Cells. Monocytes / drug effects. Myeloid Cell Leukemia Sequence 1 Protein. Neoplasm Proteins / biosynthesis. Neoplasm Proteins / genetics. Poly(ADP-ribose) Polymerase Inhibitors. Poly(ADP-ribose) Polymerases / metabolism. Proto-Oncogene Proteins c-bcl-2 / biosynthesis. Proto-Oncogene Proteins c-bcl-2 / genetics. bcl-X Protein / biosynthesis. bcl-X Protein / genetics

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  • (PMID = 17202400.001).
  • [ISSN] 0022-3565
  • [Journal-full-title] The Journal of pharmacology and experimental therapeutics
  • [ISO-abbreviation] J. Pharmacol. Exp. Ther.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Benzamides; 0 / Myeloid Cell Leukemia Sequence 1 Protein; 0 / Neoplasm Proteins; 0 / Oxazepines; 0 / PBOX-6; 0 / Piperazines; 0 / Poly(ADP-ribose) Polymerase Inhibitors; 0 / Proto-Oncogene Proteins c-bcl-2; 0 / Pyrimidines; 0 / Pyrroles; 0 / bcl-X Protein; 8A1O1M485B / Imatinib Mesylate; EC 2.4.2.30 / Poly(ADP-ribose) Polymerases; EC 2.7.10.2 / Fusion Proteins, bcr-abl
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25. Weissinger EM, Oettrich K, Evans C, Genieser HG, Schwede F, Dangers M, Dammann E, Kolb HJ, Mischak H, Ganser A, Kolch W: Activation of protein kinase A (PKA) by 8-Cl-cAMP as a novel approach for antileukaemic therapy. Br J Cancer; 2004 Jul 5;91(1):186-92
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  • [Title] Activation of protein kinase A (PKA) by 8-Cl-cAMP as a novel approach for antileukaemic therapy.
  • Activation of PKA by cAMP agonists, such as 8-Cl-cAMP activation, selectively causes rapid apoptosis in v-abl transformed fibroblasts by inhibiting the Raf-1 kinase.
  • Here we investigated whether 8-Cl-cAMP is useful for the treatment of chronic myelogenous leukaemia (CML), which is hallmarked by the expression of the p210(bcr/abl) oncogene.
  • Autologous bone marrow transplantation is a feasible alternative for patients with no suitable donor, but hampered by the risk of relapse due to the persistence of leukaemia cells in the transplant.
  • To study the effects of 8-Cl-cAMP on primary leukaemic cells, bone marrow cells (BMCs) from eight CML patients (one at diagnosis, three in chronic and four in accelerated phase) were treated.
  • Ex vivo treatment of BMCs obtained in chronic phase of CML with 100 microM 8-Cl-cAMP for 24-48 h led to the selective purging of Philadelphia Chromosome (Ph1 chromosome) without toxic side effects on BMCs from healthy donors as measured by colony-forming unit (CFU) assays.
  • BMCs from patients in accelerated phase showed selective, but incomplete elimination of Ph1 chromosome positive colony forming cells.
  • The mechanism of 8-Cl-cAMP was investigated in FDCP-mix cells transformed by p210(bcr/abl), a cell culture model for CML.
  • In summary, our results indicate that 8-Cl-cAMP could be useful to purge malignant cells from the bone marrow of patients with CML and certain other forms of leukaemias.
  • [MeSH-major] 8-Bromo Cyclic Adenosine Monophosphate / analogs & derivatives. 8-Bromo Cyclic Adenosine Monophosphate / pharmacology. Antineoplastic Agents / pharmacology. Bone Marrow Cells / physiology. Bone Marrow Purging / methods. Bone Marrow Transplantation. Cyclic AMP-Dependent Protein Kinases / pharmacology. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy

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  • [Cites] Pharmacol Ther. 2000 Aug-Sep;87(2-3):199-226 [11008001.001]
  • [Cites] J Biol Chem. 2000 Dec 15;275(50):39137-45 [10993901.001]
  • [Cites] Proc Natl Acad Sci U S A. 2001 Jul 3;98(14):7783-8 [11427728.001]
  • [Cites] Leukemia. 2002 Jul;16(7):1213-9 [12094245.001]
  • [Cites] Cancer Genet Cytogenet. 1981 Oct;4(2):157-68 [6949629.001]
  • [Cites] Eur J Immunol. 1988 Jan;18(1):97-104 [2831066.001]
  • [Cites] Nature. 1990 Jan 4;343(6253):76-9 [1688645.001]
  • [Cites] Cell. 1992 Sep 18;70(6):901-10 [1525828.001]
  • [Cites] Mol Cell Biol. 1993 Apr;13(4):2578-85 [8455630.001]
  • [Cites] Leuk Lymphoma. 1993;11 Suppl 1:45-6 [8251915.001]
  • [Cites] J Chromatogr B Biomed Appl. 1994 Aug 5;658(1):183-8 [7952122.001]
  • [Cites] Mol Cell Biol. 1995 Jan;15(1):466-75 [7799956.001]
  • [Cites] Bone Marrow Transplant. 1994;14 Suppl 3:S51-4 [7697010.001]
  • [Cites] Leuk Res. 1996 Jun;20(6):523-9 [8709625.001]
  • [Cites] Crit Rev Oncol Hematol. 1995 Nov;21(1-3):33-61 [8822496.001]
  • [Cites] Mol Cell Biol. 1997 Jun;17(6):3229-41 [9154822.001]
  • [Cites] Clin Cancer Res. 1998 Jul;4(7):1661-72 [9676840.001]
  • [Cites] Oncogene. 1998 Aug 6;17(5):667-72 [9704934.001]
  • [Cites] Chem Biol. 1999 Aug;6(8):559-68 [10421767.001]
  • [Cites] Clin Cancer Res. 1999 Jul;5(7):1682-9 [10430069.001]
  • (PMID = 15188002.001).
  • [ISSN] 0007-0920
  • [Journal-full-title] British journal of cancer
  • [ISO-abbreviation] Br. J. Cancer
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 23583-48-4 / 8-Bromo Cyclic Adenosine Monophosphate; 41941-56-4 / 8-chloro-cyclic adenosine monophosphate; 9007-49-2 / DNA; EC 2.7.11.11 / Cyclic AMP-Dependent Protein Kinases
  • [Other-IDs] NLM/ PMC2364761
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26. Bright SA, Greene LM, Greene TF, Campiani G, Butini S, Brindisi M, Lawler M, Meegan MJ, Williams DC, Zisterer DM: The novel pyrrolo-1,5-benzoxazepine, PBOX-21, potentiates the apoptotic efficacy of STI571 (imatinib mesylate) in human chronic myeloid leukaemia cells. Biochem Pharmacol; 2009 Feb 1;77(3):310-21
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  • [Title] The novel pyrrolo-1,5-benzoxazepine, PBOX-21, potentiates the apoptotic efficacy of STI571 (imatinib mesylate) in human chronic myeloid leukaemia cells.
  • The Bcr-Abl kinase inhibitor, STI571, is the first line treatment for chronic myeloid leukaemia (CML), but the recent emergence of STI571 resistance has led to the examination of combination therapies.
  • In this report, we describe how a novel non-toxic G1-arresting compound, pyrrolo-1,5-benzoxazepine (PBOX)-21, potentiates the apoptotic ability of STI571 in Bcr-Abl-positive CML cells.
  • Co-treatment of CML cells with PBOX-21 and STI571 induced more apoptosis than either drug alone in parental (K562S and LAMA84) and STI571-resistant cells lines (K562R).
  • This potentiation of apoptosis was specific to Bcr-Abl-positive leukaemia cells with no effect observed on Bcr-Abl-negative HL-60 acute myeloid leukaemia cells.
  • Apoptosis induced by PBOX-21/STI571 resulted in activation of caspase-8, cleavage of PARP and Bcl-2, upregulation of the pro-apoptotic protein Bim and a downregulation of Bcr-Abl.
  • Repression of proteins involved in Bcr-Abl transformation, the anti-apoptotic proteins Mcl-1 and Bcl-(XL) was also observed.
  • Apoptosis was significantly reduced following pre-treatment with either the general caspase inhibitor Boc-FMK or the chymotrypsin-like serine protease inhibitor TPCK, but was completely abrogated following pre-treatment with a combination of these inhibitors.
  • In conclusion, our data highlights the potential of PBOX-21 in combination with STI571 as an effective therapy against CML.
  • [MeSH-major] Antineoplastic Agents / therapeutic use. Apoptosis / drug effects. Carbamates / therapeutic use. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology. Oxazepines / therapeutic use. Piperazines / therapeutic use. Pyrimidines / therapeutic use
  • [MeSH-minor] Benzamides. Blotting, Western. Cell Line, Tumor. Down-Regulation. Drug Synergism. Flow Cytometry. Fusion Proteins, bcr-abl / metabolism. Humans. Imatinib Mesylate. Membrane Potentials / drug effects. Up-Regulation

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  • (PMID = 19014913.001).
  • [ISSN] 1873-2968
  • [Journal-full-title] Biochemical pharmacology
  • [ISO-abbreviation] Biochem. Pharmacol.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / 7-((diethylcarbamoyl)oxy)-6-p-tolylpyrrolo(2,1-d)(1,5)benzoxazepine; 0 / Antineoplastic Agents; 0 / Benzamides; 0 / Carbamates; 0 / Oxazepines; 0 / Piperazines; 0 / Pyrimidines; 8A1O1M485B / Imatinib Mesylate; EC 2.7.10.2 / Fusion Proteins, bcr-abl
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27. Stuart SA, Minami Y, Wang JY: The CML stem cell: evolution of the progenitor. Cell Cycle; 2009 May 1;8(9):1338-43
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] The CML stem cell: evolution of the progenitor.
  • The success of imatinib mesylate (STI571, Gleevec) in treating chronic myeloid leukemia (CML) is, to date, the crowning achievement of targeted molecular therapy in cancer.
  • Nearly 90% of newly diagnosed patients treated with imatinib in the chronic phase of the disease achieve a complete cytogenetic response.
  • However, more than 95% of these patients retain detectable levels of BCR-ABL mRNA and patients discontinuing imatinib therapy almost invariably relapse, demonstrating that an imatinib insensitive population of leukemia-initiating cells (LICs) persists in nearly all patients.
  • These findings underscore the need for treatments specifically targeting the leukemia-initiating population of CML cells.
  • While mounting evidence suggests that the LIC in the chronic phase of CML is the BCR-ABL positive hematopoietic stem cell, several recent publications suggest that during CML blast crisis, a granulocyte-macrophage progenitor (GMP) population also acquires LIC properties through activation of the beta-catenin pathway.
  • Characterization of these cells and evaluation of their sensitivity to imatinib is critical to our understanding and treatment of CML blast crisis.

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  • [Cites] Int J Hematol. 2008 Dec;88(5):471-5 [19039626.001]
  • [Cites] Blood. 2007 Oct 1;110(7):2242-9 [17496200.001]
  • [Cites] Blood. 2000 Feb 1;95(3):1007-13 [10648416.001]
  • [Cites] N Engl J Med. 2001 Apr 5;344(14):1031-7 [11287972.001]
  • [Cites] N Engl J Med. 2001 Apr 5;344(14):1038-42 [11287973.001]
  • [Cites] Science. 2001 Aug 3;293(5531):876-80 [11423618.001]
  • [Cites] Nature. 2001 Nov 1;414(6859):105-11 [11689955.001]
  • [Cites] Blood. 2002 Jan 1;99(1):319-25 [11756187.001]
  • [Cites] N Engl J Med. 2002 Feb 28;346(9):645-52 [11870241.001]
  • [Cites] Blood. 2002 Mar 15;99(6):1928-37 [11877262.001]
  • [Cites] Blood. 2002 May 15;99(10):3530-9 [11986204.001]
  • [Cites] Blood. 2002 Nov 1;100(9):3175-82 [12384415.001]
  • [Cites] N Engl J Med. 2003 Mar 13;348(11):994-1004 [12637609.001]
  • [Cites] Proc Natl Acad Sci U S A. 2003 Apr 1;100(7):3983-8 [12629218.001]
  • [Cites] Blood. 2003 Jun 15;101(12):4701-7 [12576334.001]
  • [Cites] N Engl J Med. 2003 Oct 9;349(15):1399-401 [14534331.001]
  • [Cites] N Engl J Med. 2003 Oct 9;349(15):1423-32 [14534335.001]
  • [Cites] Blood. 2004 Jun 1;103(11):4010-22 [14982876.001]
  • [Cites] Am J Hematol. 2004 Jul;76(3):275-8 [15224366.001]
  • [Cites] N Engl J Med. 2004 Aug 12;351(7):657-67 [15306667.001]
  • [Cites] Blood. 2004 Oct 1;104(7):2204-5 [15377577.001]
  • [Cites] Proc Natl Acad Sci U S A. 1967 Oct;58(4):1468-71 [5237880.001]
  • [Cites] Cancer Cell. 2007 Dec;12(6):528-41 [18068630.001]
  • [Cites] Science. 2007 Dec 14;318(5857):1722; author reply 1722 [18079385.001]
  • [Cites] Nature. 2008 Jan 17;451(7176):345-9 [18202660.001]
  • [Cites] Cancer Cell. 2008 Feb;13(2):153-66 [18242515.001]
  • [Cites] Cell Death Differ. 2008 Mar;15(3):504-14 [18049477.001]
  • [Cites] Cancer Cell. 2008 Jul 8;14(1):47-58 [18598943.001]
  • [Cites] Nat Rev Cancer. 2008 Oct;8(10):755-68 [18784658.001]
  • [Cites] Proc Natl Acad Sci U S A. 2008 Nov 18;105(46):17967-72 [19004799.001]
  • [Cites] Nature. 2008 Dec 4;456(7222):593-8 [19052619.001]
  • [Cites] Blood. 2008 Dec 15;112(13):4808-17 [19064740.001]
  • [Cites] Proc Natl Acad Sci U S A. 2009 Mar 10;106(10):3925-9 [19237556.001]
  • [Cites] Nature. 1973 Jun 1;243(5405):290-3 [4126434.001]
  • [Cites] J Clin Invest. 1978 Oct;62(4):815-23 [308953.001]
  • [Cites] Nature. 1980 Sep 4;287(5777):49-50 [6968038.001]
  • [Cites] Science. 1986 Jul 11;233(4760):212-4 [3460176.001]
  • [Cites] Science. 1990 Mar 2;247(4946):1079-82 [2408149.001]
  • [Cites] Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11335-8 [1763047.001]
  • [Cites] Nat Med. 1996 May;2(5):561-6 [8616716.001]
  • [Cites] Nat Med. 1997 Jul;3(7):730-7 [9212098.001]
  • [Cites] Blood. 1999 Sep 15;94(6):2056-64 [10477735.001]
  • [Cites] J Natl Cancer Inst. 1960 Jul;25:85-109 [14427847.001]
  • [Cites] Nature. 2004 Nov 18;432(7015):396-401 [15549107.001]
  • [Cites] Nat Rev Cancer. 2005 Apr;5(4):311-21 [15803157.001]
  • [Cites] Nat Med. 2005 Jun;11(6):630-7 [15908956.001]
  • [Cites] Nature. 2005 Jun 30;435(7046):1267-70 [15988530.001]
  • [Cites] Curr Opin Genet Dev. 2006 Feb;16(1):92-9 [16343892.001]
  • [Cites] Proc Natl Acad Sci U S A. 2006 Feb 21;103(8):2794-9 [16477019.001]
  • [Cites] Cancer Res. 2006 Oct 1;66(19):9339-44 [16990346.001]
  • [Cites] Nat Med. 2006 Oct;12(10):1181-4 [17013383.001]
  • [Cites] N Engl J Med. 2006 Dec 7;355(23):2408-17 [17151364.001]
  • [Cites] Blood. 2007 Jan 1;109(1):58-60 [16973963.001]
  • [Cites] Nature. 2007 Jan 4;445(7123):111-5 [17122771.001]
  • [Cites] Nature. 2007 Jan 4;445(7123):106-10 [17122772.001]
  • [Cites] Proc Natl Acad Sci U S A. 2007 Jan 16;104(3):973-8 [17210912.001]
  • [Cites] Cancer Res. 2007 Feb 1;67(3):1030-7 [17283135.001]
  • [Cites] Genes Dev. 2007 Sep 15;21(18):2283-7 [17761812.001]
  • [Cites] Cold Spring Harb Symp Quant Biol. 2008;73:461-7 [19028987.001]
  • (PMID = 19342894.001).
  • [ISSN] 1551-4005
  • [Journal-full-title] Cell cycle (Georgetown, Tex.)
  • [ISO-abbreviation] Cell Cycle
  • [Language] ENG
  • [Grant] United States / NCI NIH HHS / CA / CA043054-23; United States / NCI NIH HHS / CA / R01 CA043054; United States / NCI NIH HHS / CA / T32 CA067754; United States / NCI NIH HHS / CA / R01 CA043054-23
  • [Publication-type] Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Benzamides; 0 / Piperazines; 0 / Pyrimidines; 8A1O1M485B / Imatinib Mesylate
  • [Other-IDs] NLM/ NIHMS159789; NLM/ PMC2792634
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28. Fischer T: [Results up to now of administration of STI-571 (Glivec) in recurrence after allogenic and autologous stem cell transplantation in chronic myeloid leukemia]. Med Klin (Munich); 2002 Jan 15;97 Suppl 1:22-7
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] [Results up to now of administration of STI-571 (Glivec) in recurrence after allogenic and autologous stem cell transplantation in chronic myeloid leukemia].
  • [Transliterated title] Bisherige Ergebnisse beim Einsatz von STI-571 (Glivec) im Rezidiv nach allogener bzw. autologer Stammzelltransplantation bei CML.
  • BACKGROUND: Gleevec (STI-571) is s selective inhibitor of the bcr/abl tyrosine kinase.
  • Recent phase I and phase II studies in patients with bcr/abl positive CML and ALL showed a low rate of grade III/IV toxicity and good clinical efficacy.
  • THERAPY AND RESULTS: 18 of 18 patients with cytogenetic and/or hematologic relapse in chronic phase CML post autologous stem cell transplantation achieved a complete hematologic remission upon therapy with Gleevec.
  • The cytogenetic response rate was 75% with a complete cytogenetic response rate of 50%.
  • After allogeneic stem cell transplantation, patients in cytogenetic or hematologic relapse also experienced high hematologic and cytogenetic response rates upon therapy with Gleevec.
  • No symptoms of chronic extensive or > grade I acute GvHD could be observed.
  • Grade III/IV granulocytopenia and/or thrombopenia could be observed in 50% of patients with transformed phases of CML.
  • CONCLUSION: These results show a new approach in treatment of patients with Philadelphia-chromosome-positive leukemia relapsing post autologous or allogeneic stem cell transplantation.
  • The data suggest that early start of STI-571 therapy in MRD-positive patients is a promising approach.
  • Recently, a multicenter phase II study to evaluate the toxicity and efficacy of Gleevec in CML patients with minimal residual disease post allogeneic transplantation was started.
  • [MeSH-major] Antineoplastic Agents / therapeutic use. Enzyme Inhibitors / therapeutic use. Hematopoietic Stem Cell Transplantation. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy. Piperazines / therapeutic use. Pyrimidines / therapeutic use
  • [MeSH-minor] Adolescent. Adult. Benzamides. Child. Clinical Trials as Topic. Female. Humans. Imatinib Mesylate. Male. Middle Aged. Remission Induction. Treatment Outcome


29. Burchert A: Roots of imatinib resistance: a question of self-renewal? Drug Resist Updat; 2007 Aug-Oct;10(4-5):152-61
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • The BCR-ABL-fusion gene is critical for the development of chronic myeloid leukemia (CML) and BCR-ABL positive acute lymphatic leukemia (Ph+ ALL).
  • Blocking BCR-ABL by the ABL tyrosine kinase inhibitor imatinib mesylate (IM, Gleevec) is clinically highly efficient.
  • Treatment response is unfortunately compromised by the emergence of IM resistance, which is regularly seen in accelerated and blastic phase of CML (CML-AP/BP) and in Ph+ ALL.
  • BCR-ABL kinase domain mutations are then considered the causative mechanism of IM resistance, because 50-60% of the IM resistant patients harbour such mutations.
  • In contrast, IM resistance arises very rarely in patients that are treated with IM in early chronic phase of CML.
  • This implies that BCR-ABL independent factors such as the cellular context of BCR-ABL expression and stage of disease decisively control the evolution of IM resistance.
  • In line with this, novel Abl-kinase inhibitors such as dasatinib (DA) or nilotinib (NI) - although capable of inhibiting most of the BCR/-BL kinase mutants - still often fail to overcome resistance and do mostly not induce durable cytogenetic responses in IM resistant CML-AP/BC and Ph+ ALL patients.
  • On the basis of available evidence it is proposed here that alternative genetic aberrations, which synergize with BCR-ABL to enable leukemic self-renewal are of causal importance for the evolution of clinical kinase inhibitor resistance.
  • This model has clinical implications as it implies that even highly potent Abl-kinase inhibition can not target the genetic basis of IM resistance and will also not resolve the problem of Abl-kinase inhibitor resistance.
  • [MeSH-major] Piperazines / therapeutic use. Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy. Protein-Tyrosine Kinases / antagonists & inhibitors. Pyrimidines / therapeutic use
  • [MeSH-minor] Antineoplastic Agents / pharmacology. Antineoplastic Agents / therapeutic use. Benzamides. Drug Resistance, Neoplasm / genetics. Fusion Proteins, bcr-abl. Humans. Imatinib Mesylate. Models, Biological. Mutation

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  • (PMID = 17683977.001).
  • [ISSN] 1368-7646
  • [Journal-full-title] Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy
  • [ISO-abbreviation] Drug Resist. Updat.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't; Review
  • [Publication-country] Scotland
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Benzamides; 0 / Piperazines; 0 / Pyrimidines; 8A1O1M485B / Imatinib Mesylate; EC 2.7.10.1 / Protein-Tyrosine Kinases; EC 2.7.10.2 / Fusion Proteins, bcr-abl
  • [Number-of-references] 104
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30. Radojkovic M, Ristic S, Pavlovic S, Colovic M: Molecular response to imatinib in patient with Ph negative p190 BCR-ABL transcript positive chronic myeloid leukemia with cyclic leukocytosis. Leuk Res; 2009 Jun;33(6):e10-2
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Molecular response to imatinib in patient with Ph negative p190 BCR-ABL transcript positive chronic myeloid leukemia with cyclic leukocytosis.
  • An atypical case of Philadelphia (Ph) negative, e1a2 BCR-ABL transcript positive chronic myeloid leukemia (CML) characterized with cyclic periodic leukocytosis and spontaneous remissions is reported.
  • So far, only few Ph positive CML patients expressing p190 BCR-ABL protein and different clinical characteristics and treatment have been described in the literature.
  • This is the first report of Philadelphia negative, p190 BCR-ABL positive CML with cyclic spontaneous oscillation of white blood cell count (WBC), and excellent response to imatinib treatment.
  • [MeSH-major] Antineoplastic Agents / therapeutic use. Genes, abl. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy. Leukocytosis. Piperazines / therapeutic use. Pyrimidines / therapeutic use. RNA, Messenger / genetics


31. Koldehoff M, Beelen DW, Trenschel R, Steckel NK, Peceny R, Ditschkowski M, Ottinger H, Elmaagacli AH: Outcome of hematopoietic stem cell transplantation in patients with atypical chronic myeloid leukemia. Bone Marrow Transplant; 2004 Dec;34(12):1047-50
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Outcome of hematopoietic stem cell transplantation in patients with atypical chronic myeloid leukemia.
  • Atypical chronic myeloid leukemia (aCML) occurs rarely and is associated with a poor prognosis when treated with conventional chemotherapy.
  • Analysis of the leukocyte chimerism of peripheral white blood cells and bone marrow buffy coat cells by VNTR-polymerase chain reaction (PCR) and single-nucleotide polymorphism real-time PCR revealed complete chimerism in all patients who had received an allogeneic transplant.
  • All other patients were alive at the time of analysis.
  • Our findings suggest that the outcome of allogeneic or syngeneic transplantation in patients with aCML may not be worse than the outcome of transplantation for BCR-ABL-positive CML.
  • [MeSH-major] Hematopoietic Stem Cell Transplantation / methods. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / therapy
  • [MeSH-minor] Adult. Female. Follow-Up Studies. Graft vs Host Disease. Humans. Male. Middle Aged. Opportunistic Infections. Remission Induction. Retrospective Studies. Tissue Donors. Transplantation Chimera. Transplantation, Homologous. Transplantation, Isogeneic. Treatment Outcome






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