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1. Abou Mourad YR, Fernandez HF, Kharfan-Dabaja MA: Allogeneic hematopoietic cell transplantation for adult Philadelphia-positive acute lymphoblastic leukemia in the era of tyrosine kinase inhibitors. Biol Blood Marrow Transplant; 2008 Sep;14(9):949-58
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  • [Title] Allogeneic hematopoietic cell transplantation for adult Philadelphia-positive acute lymphoblastic leukemia in the era of tyrosine kinase inhibitors.
  • Allogeneic hematopoietic cell transplantation in first complete remission (CR1) is considered the standard of care, and the only established therapy that offers a possibility of cure for patients with Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL).
  • [MeSH-major] Algorithms. Hematopoietic Stem Cell Transplantation. Philadelphia Chromosome. Piperazines / therapeutic use. Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy. Protein Kinase Inhibitors / therapeutic use. Pyrimidines / therapeutic use

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  • (PMID = 18721758.001).
  • [ISSN] 1523-6536
  • [Journal-full-title] Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
  • [ISO-abbreviation] Biol. Blood Marrow Transplant.
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Benzamides; 0 / Glucocorticoids; 0 / Piperazines; 0 / Protein Kinase Inhibitors; 0 / Pyrimidines; 8A1O1M485B / Imatinib Mesylate
  • [Number-of-references] 57
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2. Lee S, Kim SH, Choi SM, Lee DG, Kim SY, Lee JW, Min WS, Shin WS, Kim CC: Cytomegalovirus ventriculoencephalitis after unrelated double cord blood stem cell transplantation with an alemtuzumab-containing preparative regimen for Philadelphia-positive acute lymphoblastic leukemia. J Korean Med Sci; 2010 Apr;25(4):630-3
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  • [Title] Cytomegalovirus ventriculoencephalitis after unrelated double cord blood stem cell transplantation with an alemtuzumab-containing preparative regimen for Philadelphia-positive acute lymphoblastic leukemia.
  • Despite the prophylaxis and preemptive strategies using potent antiviral agents, cytomegalovirus (CMV) remains a major infectious cause of morbidity and mortality in allogeneic stem cell transplantation (SCT) recipients.
  • Delayed immune reconstitution after SCT, such as cord blood and T-cell depleted SCT with the use of alemtuzumab, has been associated with an increased frequency of CMV disease as well as CMV reactivation.
  • We report a case of CMV ventriculoencephalitis after unrelated double cord blood SCT with an alemtuzumab-containing preparative regimen for Philadelphia-positive acute lymphoblastic leukemia.
  • [MeSH-major] Antibodies, Monoclonal / therapeutic use. Antibodies, Neoplasm / therapeutic use. Antineoplastic Agents / therapeutic use. Cord Blood Stem Cell Transplantation / adverse effects. Cytomegalovirus Infections / drug therapy. Cytomegalovirus Infections / etiology. Encephalitis. Precursor Cell Lymphoblastic Leukemia-Lymphoma

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  • (PMID = 20358010.001).
  • [ISSN] 1598-6357
  • [Journal-full-title] Journal of Korean medical science
  • [ISO-abbreviation] J. Korean Med. Sci.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] Korea (South)
  • [Chemical-registry-number] 0 / Antibodies, Monoclonal; 0 / Antibodies, Monoclonal, Humanized; 0 / Antibodies, Neoplasm; 0 / Antineoplastic Agents; 3A189DH42V / alemtuzumab
  • [Other-IDs] NLM/ PMC2844610
  • [Keywords] NOTNLM ; Alemtuzumab / Cord Blood Stem Cell Transplantation / Cytomegalovirus / Encephalitis / Leukemia
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3. Martin V, Agirre X, Jiménez-Velasco A, José-Eneriz ES, Cordeu L, Gárate L, Vilas-Zornoza A, Castillejo JA, Heiniger A, Prósper F, Torres A, Roman-Gomez J: Methylation status of Wnt signaling pathway genes affects the clinical outcome of Philadelphia-positive acute lymphoblastic leukemia. Cancer Sci; 2008 Sep;99(9):1865-8
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  • [Title] Methylation status of Wnt signaling pathway genes affects the clinical outcome of Philadelphia-positive acute lymphoblastic leukemia.
  • The clinical significance of aberrant promoter methylation of the canonical Wnt pathway antagonist genes (sFRP1, sFRP2, sFRP4, sFRP5, Wif1, Dkk3, and Hdpr1) and also putative tumor-suppressor gene Wnt5a, belonging to the non-canonical Wnt signaling pathway, was investigated in a large series of 75 patients with Philadelphia chromosome-positive acute lymphoblastic leukemia by methylation-specific polymerase chain reaction.
  • Abnormal DNA methylation of promoter-associated CpG islands in the Wnt signaling pathway is very common in Philadelphia chromosome-positive acute lymphoblastic leukemia and potentially defines subgroups with distinct clinical characteristics.
  • [MeSH-major] DNA Methylation. Philadelphia Chromosome. Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics. Wnt Proteins / genetics

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  • (PMID = 18549404.001).
  • [ISSN] 1349-7006
  • [Journal-full-title] Cancer science
  • [ISO-abbreviation] Cancer Sci.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Wnt Proteins
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4. Wassmann B, Pfeifer H, Goekbuget N, Beelen DW, Beck J, Stelljes M, Bornhäuser M, Reichle A, Perz J, Haas R, Ganser A, Schmid M, Kanz L, Lenz G, Kaufmann M, Binckebanck A, Brück P, Reutzel R, Gschaidmeier H, Schwartz S, Hoelzer D, Ottmann OG: Alternating versus concurrent schedules of imatinib and chemotherapy as front-line therapy for Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL). Blood; 2006 Sep 1;108(5):1469-77
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  • [Title] Alternating versus concurrent schedules of imatinib and chemotherapy as front-line therapy for Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL).
  • The best strategy for incorporating imatinib in front-line treatment of Ph+ acute lymphoblastic leukemia (ALL) has not been established.
  • Coadministration of imatinib and induction cycle 2 (INDII) resulted in a complete remission (CR) rate of 95% and polymerase chain reaction (PCR) negativity for BCR-ABL in 52% of patients, compared with 19% in patients in the alternating treatment cohort (P = .01).
  • In each cohort, 77% of patients underwent allogeneic stem cell transplantation (SCT) in first CR (CR1).
  • [MeSH-major] Antineoplastic Agents / therapeutic use. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Piperazines / therapeutic use. Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy. Pyrimidines / therapeutic use
  • [MeSH-minor] Adult. Aged. Benzamides. Bone Marrow / pathology. Drug Administration Schedule. Drug Therapy, Combination. Female. Fusion Proteins, bcr-abl / deficiency. Fusion Proteins, bcr-abl / genetics. Humans. Imatinib Mesylate. Male. Middle Aged. Polymerase Chain Reaction. Probability. Remission Induction. Survival Analysis. Transcription, Genetic. Treatment Outcome


5. Vega-Ruiz A, O'Brien S, Cortes J, Kebriaei P, Thomas D, Kantarjian H, Ravandi F: Secondary myelodysplastic syndrome in a patient with Philadelphia-positive acute lymphoblastic leukemia after achieving a major molecular response with hyperCVAD plus imatinib mesylate. Leuk Res; 2008 Sep;32(9):1468-71
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  • [Title] Secondary myelodysplastic syndrome in a patient with Philadelphia-positive acute lymphoblastic leukemia after achieving a major molecular response with hyperCVAD plus imatinib mesylate.
  • The addition of imatinib to high-intensity chemotherapy has improved the outcome of patients with Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL).
  • Development of new clonal abnormalities in complete cytogenetic remission after treatment with imatinib has been reported in patients with chronic myeloid leukemia but not in patients with Ph-positive ALL.
  • Here, we present a patient with Ph-positive ALL who received hyperCVAD plus imatinib and achieved hematologic, cytogenetic, and major molecular responses.
  • [MeSH-major] Antineoplastic Agents / therapeutic use. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Central Nervous System Neoplasms / etiology. Myelodysplastic Syndromes / etiology. Neoplasms, Second Primary / etiology. Piperazines / therapeutic use. Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy. Pyrimidines / therapeutic use
  • [MeSH-minor] Benzamides. Cyclophosphamide / therapeutic use. Cytogenetic Analysis. Dexamethasone / therapeutic use. Doxorubicin / therapeutic use. Female. Hematopoietic Stem Cell Transplantation. Humans. Imatinib Mesylate. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / etiology. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / therapy. Middle Aged. Protein-Tyrosine Kinases / antagonists & inhibitors. Remission Induction. Treatment Outcome. Vincristine / therapeutic use


6. Li YN, Zou DH, Gu M, Mi YC, Wang JX, Qiu LG: [The role of BCR/ABL isoforms in the presentations and outcome of Philadelphia-positive acute lymphoblastic leukemia in adult patients]. Zhonghua Nei Ke Za Zhi; 2009 Jun;48(6):481-4
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  • [Title] [The role of BCR/ABL isoforms in the presentations and outcome of Philadelphia-positive acute lymphoblastic leukemia in adult patients].
  • OBJECTIVE: To investigate the difference of clinical characteristics and outcomes between different isoforms of BCR/ABL in adults with Philadelphia-positive acute lymphoblastic leukemia (ALL).
  • The difference of clinical characteristics between different subgroups of BCR/ABL was compared and their relation with outcomes was studied.
  • RESULTS: The median age of the 106 patients was 34 years and the median white blood cell count at baseline was 28.5 x 10(9)/L.
  • CONCLUSION: Majority of the adults with Ph+ ALL is p190 positive and patients with p210 have older age, higher BPC and more frequent occurrence of splenomegaly, while there is no significant difference between p190 group and p210 group in CR rate, RFS and OS.
  • [MeSH-major] Fusion Proteins, bcr-abl / genetics. Precursor Cell Lymphoblastic Leukemia-Lymphoma / diagnosis. Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics
  • [MeSH-minor] Adolescent. Adult. Female. Humans. Male. Middle Aged. Philadelphia Chromosome. Prognosis. Protein Isoforms / genetics. Retrospective Studies. Young Adult

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  • (PMID = 19954044.001).
  • [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; Research Support, Non-U.S. Gov't
  • [Publication-country] China
  • [Chemical-registry-number] 0 / Protein Isoforms; 0 / abl-bcr fusion protein, human; EC 2.7.10.2 / Fusion Proteins, bcr-abl
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7. Tiribelli M, Sperotto A, Candoni A, Simeone E, Buttignol S, Fanin R: Nilotinib and donor lymphocyte infusion in the treatment of Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL) relapsing after allogeneic stem cell transplantation and resistant to imatinib. Leuk Res; 2009 Jan;33(1):174-7
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  • [Title] Nilotinib and donor lymphocyte infusion in the treatment of Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL) relapsing after allogeneic stem cell transplantation and resistant to imatinib.
  • Prognosis of patients with Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL) relapsing after allogeneic stem cell transplantation (SCT) is dismal.
  • [MeSH-major] Antineoplastic Agents / therapeutic use. Lymphocyte Transfusion. Philadelphia Chromosome. Piperazines / therapeutic use. Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy. Pyrimidines / therapeutic use. Stem Cell Transplantation

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  • (PMID = 18471874.001).
  • [ISSN] 0145-2126
  • [Journal-full-title] Leukemia research
  • [ISO-abbreviation] Leuk. Res.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 0 / 4-methyl-N-(3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl)-3-((4-pyridin-3-ylpyrimidin-2-yl)amino)benzamide; 0 / Antineoplastic Agents; 0 / Benzamides; 0 / Piperazines; 0 / Pyrimidines; 8A1O1M485B / Imatinib Mesylate
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8. Delannoy A, Delabesse E, Lhéritier V, Castaigne S, Rigal-Huguet F, Raffoux E, Garban F, Legrand O, Bologna S, Dubruille V, Turlure P, Reman O, Delain M, Isnard F, Coso D, Raby P, Buzyn A, Caillères S, Darre S, Fohrer C, Sonet A, Bilhou-Nabera C, Béné MC, Dombret H, Berthaud P, Thomas X: Imatinib and methylprednisolone alternated with chemotherapy improve the outcome of elderly patients with Philadelphia-positive acute lymphoblastic leukemia: results of the GRAALL AFR09 study. Leukemia; 2006 Sep;20(9):1526-32
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  • [Title] Imatinib and methylprednisolone alternated with chemotherapy improve the outcome of elderly patients with Philadelphia-positive acute lymphoblastic leukemia: results of the GRAALL AFR09 study.
  • Acute lymphoblastic leukemia (ALL) in the elderly is characterized by its ominous prognosis.
  • On the other hand, imatinib has demonstrated remarkable, although transient, activity in relapsed and refractory Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL), which prompted us to assess the use of imatinib in previously untreated elderly patients.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Methylprednisolone / therapeutic use. Philadelphia Chromosome. Piperazines / therapeutic use. Precursor Cell Lymphoblastic Leukemia-Lymphoma / surgery. Pyrimidines / therapeutic use. Treatment Outcome
  • [MeSH-minor] Aged. Benzamides. Disease-Free Survival. Humans. Imatinib Mesylate. Stem Cell Transplantation

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  • (PMID = 16838024.001).
  • [ISSN] 0887-6924
  • [Journal-full-title] Leukemia
  • [ISO-abbreviation] Leukemia
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Benzamides; 0 / Piperazines; 0 / Pyrimidines; 8A1O1M485B / Imatinib Mesylate; X4W7ZR7023 / Methylprednisolone
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9. Li Y, Qiu L, Zou D, Zhao Y, Mi Y, Wang J: Additional chromosomal abnormalities and their prognostic significance in adult Philadelphia-positive acute lymphoblastic leukemia: with or without imatinib in chemotherapy. Ann Hematol; 2009 Nov;88(11):1069-77
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  • [Title] Additional chromosomal abnormalities and their prognostic significance in adult Philadelphia-positive acute lymphoblastic leukemia: with or without imatinib in chemotherapy.
  • The study analyzed the characteristics and prognostic significance of additional chromosomal abnormalities in 110 Chinese adults with Philadelphia chromosome-positive (Ph-positive) acute lymphoblastic leukemia (ALL).
  • Fifty of 110 patients (45.5%) had at least one normal metaphase cell in their chromosome preparations at diagnosis.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Chromosome Aberrations. Piperazines / therapeutic use. Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics. Pyrimidines / therapeutic use. Salvage Therapy
  • [MeSH-minor] 6-Mercaptopurine / administration & dosage. Adolescent. Adult. Asparaginase / administration & dosage. Benzamides. Cyclophosphamide / administration & dosage. Cytarabine / administration & dosage. Daunorubicin / administration & dosage. Disease-Free Survival. Etoposide / administration & dosage. Female. Fusion Proteins, bcr-abl / antagonists & inhibitors. Humans. Imatinib Mesylate. Kaplan-Meier Estimate. Male. Methotrexate / administration & dosage. Middle Aged. Mitoxantrone / administration & dosage. Prednisone / administration & dosage. Prognosis. Vincristine / administration & dosage. Vindesine / administration & dosage. Young Adult

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  • (PMID = 19277658.001).
  • [ISSN] 1432-0584
  • [Journal-full-title] Annals of hematology
  • [ISO-abbreviation] Ann. Hematol.
  • [Language] eng
  • [Publication-type] Comparative Study; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] Germany
  • [Chemical-registry-number] 0 / Benzamides; 0 / Piperazines; 0 / Pyrimidines; 04079A1RDZ / Cytarabine; 5J49Q6B70F / Vincristine; 6PLQ3CP4P3 / Etoposide; 8A1O1M485B / Imatinib Mesylate; 8N3DW7272P / Cyclophosphamide; BZ114NVM5P / Mitoxantrone; E7WED276I5 / 6-Mercaptopurine; EC 2.7.10.2 / Fusion Proteins, bcr-abl; EC 3.5.1.1 / Asparaginase; RSA8KO39WH / Vindesine; VB0R961HZT / Prednisone; YL5FZ2Y5U1 / Methotrexate; ZS7284E0ZP / Daunorubicin
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10. Rea D, Legros L, Raffoux E, Thomas X, Turlure P, Maury S, Dupriez B, Pigneux A, Choufi B, Reman O, Stéphane D, Royer B, Vigier M, Ojeda-Uribe M, Recher C, Dombret H, Huguet F, Rousselot P, Intergroupe Français des Leucémies Myéloïdes Chronique, Group for Research in Adult Acute Lymphoblastic Leukemia: High-dose imatinib mesylate combined with vincristine and dexamethasone (DIV regimen) as induction therapy in patients with resistant Philadelphia-positive acute lymphoblastic leukemia and lymphoid blast crisis of chronic myeloid leukemia. Leukemia; 2006 Mar;20(3):400-3
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  • [Title] High-dose imatinib mesylate combined with vincristine and dexamethasone (DIV regimen) as induction therapy in patients with resistant Philadelphia-positive acute lymphoblastic leukemia and lymphoid blast crisis of chronic myeloid leukemia.
  • Imatinib combined with high-dose chemotherapy is now becoming the gold standard for treatment of Philadelphia chromosome-positive acute leukemias.
  • Thirty-one patients (18 relapsing or refractory Ph+ acute lymphoblastic leukemias and 13 lymphoid blast crisis chronic myelogenous leukemias) were enrolled.
  • The median bcr-abl/abl ratio after the induction course was 0.1%.
  • Nine out of 19 patients under 55 years received allogenic stem cell transplantation after a median time of 78 days post-CR.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Blast Crisis / drug therapy. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy. Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy


11. Verstovsek S, Golemovic M, Kantarjian H, Manshouri T, Estrov Z, Manley P, Sun T, Arlinghaus RB, Alland L, Dugan M, Cortes J, Giles F, Beran M: AMN107, a novel aminopyrimidine inhibitor of p190 Bcr-Abl activation and of in vitro proliferation of Philadelphia-positive acute lymphoblastic leukemia cells. Cancer; 2005 Sep 15;104(6):1230-6
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  • [Title] AMN107, a novel aminopyrimidine inhibitor of p190 Bcr-Abl activation and of in vitro proliferation of Philadelphia-positive acute lymphoblastic leukemia cells.
  • BACKGROUND: Previous studies have shown that patients with Bcr-Abl-positive acute lymphoblastic leukemia (ALL) either have primary disease that is refractory to imatinib mesylate or develop disease recurrence after an initial response.
  • METHODS: The authors investigated the effects of a newly designed Bcr-Abl inhibitor, AMN107, by comparing its in vitro inhibitory potency on p190 Bcr-Abl ALL cell lines with that of imatinib.
  • RESULTS: In two Philadelphia (Ph)-positive ALL cell lines, AMN107 was found to be 30-40 times more potent than imatinib in inhibiting cellular proliferation.
  • AMN107 was also more effective than imatinib in inhibiting phosphorylation of p190 Bcr-Abl tyrosine kinase in cell lines and primary ALL cells.
  • The inhibition of cellular proliferation was associated with the induction of apoptosis in only one of the cell lines.
  • No activity was observed in cell lines lacking the BCR-ABL genotype.
  • CONCLUSIONS: The results of the current study suggest the superior potency of AMN107 compared with imatinib in Ph-positive ALL and support clinical trials of AMN107 in patients with Ph-positive ALL.
  • [MeSH-major] Antineoplastic Agents / pharmacology. Fusion Proteins, bcr-abl / antagonists & inhibitors. Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy. Pyrimidines / pharmacology
  • [MeSH-minor] Apoptosis / drug effects. Benzamides. Caspase 3. Caspases / metabolism. Cell Cycle / drug effects. Cell Line, Tumor. Cell Proliferation / drug effects. Humans. Imatinib Mesylate. Phosphorylation. Piperazines / pharmacology

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  • [Copyright] Copyright 2005 American Cancer Society.
  • (PMID = 16078266.001).
  • [ISSN] 0008-543X
  • [Journal-full-title] Cancer
  • [ISO-abbreviation] Cancer
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / 4-methyl-N-(3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl)-3-((4-pyridin-3-ylpyrimidin-2-yl)amino)benzamide; 0 / Antineoplastic Agents; 0 / Benzamides; 0 / Piperazines; 0 / Pyrimidines; 8A1O1M485B / Imatinib Mesylate; EC 2.7.10.2 / Fusion Proteins, bcr-abl; EC 3.4.22.- / CASP3 protein, human; EC 3.4.22.- / Caspase 3; EC 3.4.22.- / Caspases
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12. Cimino G, Pane F, Elia L, Finolezzi E, Fazi P, Annino L, Meloni G, Mancini M, Tedeschi A, Di Raimondo F, Specchia G, Fioritoni G, Leoni P, Cuneo A, Mecucci C, Saglio G, Mandelli F, Foà R, GIMEMA Leukemia Working Party: The role of BCR/ABL isoforms in the presentation and outcome of patients with Philadelphia-positive acute lymphoblastic leukemia: a seven-year update of the GIMEMA 0496 trial. Haematologica; 2006 Mar;91(3):377-80
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  • [Title] The role of BCR/ABL isoforms in the presentation and outcome of patients with Philadelphia-positive acute lymphoblastic leukemia: a seven-year update of the GIMEMA 0496 trial.
  • To verify the potential clinical and prognostic value of BCR/ABL isoforms, we analyzed 101 consecutive adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia enrolled in the GIMEMA 0496 trial between October 1996 and December 1999.
  • A p190 or p210 with or without p190 BCR/ABL transcript was documented in 59 (58.5%) and 42 cases (41.5%), respectively.
  • At diagnosis, a white cell count <16 x 10(9)/L and a higher level of CD34 and CD33 expression were associated with the p190 BCR/ABL transcript (p<0.05, p=0.009 and p=0.03, respectively).
  • Fifty-two patients underwent intensive re-induction treatment, which was followed by stem cell transplant consolidation in the 36 in persistent complete remission (allogeneic = 20 patients; autologous = 16 patients).
  • Response rates to induction therapies were similar in the two BCR/ABL isoform groups.
  • [MeSH-major] Fusion Proteins, bcr-abl / physiology. Multicenter Studies as Topic. Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics. Randomized Controlled Trials as Topic

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  • (PMID = 16531262.001).
  • [ISSN] 1592-8721
  • [Journal-full-title] Haematologica
  • [ISO-abbreviation] Haematologica
  • [Language] eng
  • [Publication-type] Comparative Study; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] Italy
  • [Chemical-registry-number] 0 / Genetic Markers; 0 / Protein Isoforms; EC 2.7.10.2 / Fusion Proteins, bcr-abl
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13. Iacobucci I, Lonetti A, Messa F, Cilloni D, Arruga F, Ottaviani E, Paolini S, Papayannidis C, Piccaluga PP, Giannoulia P, Soverini S, Amabile M, Poerio A, Saglio G, Pane F, Berton G, Baruzzi A, Vitale A, Chiaretti S, Perini G, Foà R, Baccarani M, Martinelli G: Expression of spliced oncogenic Ikaros isoforms in Philadelphia-positive acute lymphoblastic leukemia patients treated with tyrosine kinase inhibitors: implications for a new mechanism of resistance. Blood; 2008 Nov 1;112(9):3847-55
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  • [Title] Expression of spliced oncogenic Ikaros isoforms in Philadelphia-positive acute lymphoblastic leukemia patients treated with tyrosine kinase inhibitors: implications for a new mechanism of resistance.
  • We sought to determine whether molecular abnormalities involving the IKZF1 gene were associated with resistance to tyrosine kinase inhibitors (TKIs) in Ph+ acute lymphoblastic leukemia (ALL) patients.
  • There was a strong correlation between nonfunctional Ikaros isoforms and BCR-ABL transcript level.
  • Furthermore, patient-derived leukemia cells expressed oncogenic Ikaros isoforms before TKI treatment, but not during response to TKIs, and predominantly at the time of relapse.
  • [MeSH-major] Ikaros Transcription Factor / genetics. Philadelphia Chromosome. Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy. Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics
  • [MeSH-minor] Adolescent. Adult. Aged. Alternative Splicing. Antineoplastic Agents / pharmacokinetics. Base Sequence. Benzamides. Cell Line, Tumor. DNA Primers / genetics. DNA, Neoplasm / genetics. Dasatinib. Drug Resistance, Neoplasm / genetics. Genes, abl. Humans. Imatinib Mesylate. Middle Aged. Mutation. Piperazines / pharmacology. Protein Isoforms / genetics. Protein Kinase Inhibitors / pharmacology. Protein-Tyrosine Kinases / antagonists & inhibitors. Pyrimidines / pharmacology. Thiazoles / pharmacology

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  • [ErratumIn] Blood. 2010 Sep 23;116(12):2196
  • (PMID = 18650450.001).
  • [ISSN] 1528-0020
  • [Journal-full-title] Blood
  • [ISO-abbreviation] Blood
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Benzamides; 0 / DNA Primers; 0 / DNA, Neoplasm; 0 / IKZF1 protein, human; 0 / Piperazines; 0 / Protein Isoforms; 0 / Protein Kinase Inhibitors; 0 / Pyrimidines; 0 / Thiazoles; 148971-36-2 / Ikaros Transcription Factor; 8A1O1M485B / Imatinib Mesylate; EC 2.7.10.1 / Protein-Tyrosine Kinases; RBZ1571X5H / Dasatinib
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14. Sindt A, Deau B, Brahim W, Staal A, Visanica S, Villarese P, Rault JP, Macintyre E, Delabesse E: Acute monocytic leukemia with coexpression of minor BCR-ABL1 and PICALM-MLLT10 fusion genes along with overexpression of HOXA9. Genes Chromosomes Cancer; 2006 Jun;45(6):575-82
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  • [Title] Acute monocytic leukemia with coexpression of minor BCR-ABL1 and PICALM-MLLT10 fusion genes along with overexpression of HOXA9.
  • The t(9;22)(q34;q11) translocation occurs in chronic myeloid leukemia (CML) and adult B-cell acute lymphoblastic leukemia (ALL), leading to fusion of BCR to ABL1 and constitutive activation of ABL1 tyrosine kinase activity.
  • The main BCR-ABL1 breakpoints result in P190 BCR-ABL1 or P210 BCR-ABL1 fusion proteins.
  • The latter is found in almost all cases of CML and in one third of the cases of t(9;22)-positive adult B-ALL.
  • P190 BCR-ABL1 is found in the remaining two thirds of t(9;22)-positive adult B-ALL cases but only exceptionally in CML.
  • We describe here the first case of t(9;22)(q34;q11) associated with t(10;11)(p13;q14) in acute monocytic leukemia.
  • The recurrent t(10;11)(p13;q14) translocation, usually found in acute myeloid leukemia (AML) and T-ALL, merges PICALM to MLLT10.
  • RT-PCR enabled identification of PICALM-MLLT10 and BCR-ABL1 e1-a2 fusion transcripts; in the context of chronic and acute myeloid leukemia, the latter usually has a monocytic presentation.
  • We also identified overexpression of HOXA9, a gene essential to myeloid differentiation that is expressed in PICALM-MLLT10 and MLL-rearranged acute leukemias.
  • This case fits with and extends a recently proposed multistage AML model in which constitutive activation of tyrosine kinases by mutations (BCR-ABL1) are associated with deregulation of transcription factors central to myeloid differentiation (HOXA9 secondary to PICALM-MLLT10).
  • [MeSH-major] Fusion Proteins, bcr-abl / metabolism. Gene Expression Regulation, Neoplastic. Homeodomain Proteins / metabolism. Leukemia, Monocytic, Acute / genetics. Oncogene Proteins, Fusion / metabolism

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  • [Copyright] (c) 2006 Wiley-Liss, Inc.
  • (PMID = 16518848.001).
  • [ISSN] 1045-2257
  • [Journal-full-title] Genes, chromosomes & cancer
  • [ISO-abbreviation] Genes Chromosomes Cancer
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Homeodomain Proteins; 0 / MLLT10 protein, human; 0 / Monomeric Clathrin Assembly Proteins; 0 / Oncogene Proteins, Fusion; 0 / PICALM protein, human; 0 / PICALM-MLLT10 fusion protein, human; 0 / Transcription Factors; 0 / homeobox protein HOXA9; EC 2.7.10.1 / FLT3 protein, human; EC 2.7.10.1 / fms-Like Tyrosine Kinase 3; EC 2.7.10.2 / Fusion Proteins, bcr-abl
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15. Czyz A, Lewandowski K, Kroll R, Komarnicki M: Dasatinib-induced complete molecular response after allogeneic hematopoietic stem cell transplantation in Philadelphia chromosome-positive acute lymphoblastic leukemia resistant to prior imatinib-containing regimen: a case report and discussion. Med Oncol; 2010 Dec;27(4):1123-6
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  • [Title] Dasatinib-induced complete molecular response after allogeneic hematopoietic stem cell transplantation in Philadelphia chromosome-positive acute lymphoblastic leukemia resistant to prior imatinib-containing regimen: a case report and discussion.
  • Presence of the Philadelphia chromosome in acute lymphoblastic leukemia is the single most adverse prognostic marker associated with high risk of disease relapse and poor prognosis.
  • Allogeneic haematopoietic stem cell transplantation is considered as the only curative option in adults with Philadelphia-positive acute lymphoblastic leukemia, but relapse remains the main cause of treatment failure.
  • Incorporation of tyrosine kinase inhibitors into transplantation strategy in patients with Philadelphia-positive acute lymphoblastic leukemia may improve prognosis of the disease.
  • Imatinib combined with conventional chemotherapy and used in conjunction with allogeneic hematopoietic stem cell transplantation has improved long-term survival rates.
  • The more potent multikinase inhibitor dasatinib has shown enhanced activity in Philadelphia-positive acute lymphoblastic leukemia and has been approved for the treatment of adults with resistance or intolerance to prior imatinib therapy.
  • Here, we present a case of Philadelphia-positive acute lymphoblastic leukemia primary resistant to imatinib combined with chemotherapy.
  • Subsequently, the patient underwent allogeneic hematopoietic stem cell transplantation as a salvage therapy.
  • [MeSH-major] Drug Resistance, Neoplasm. Hematopoietic Stem Cell Transplantation. Piperazines / adverse effects. Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy. Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy. Pyrimidines / adverse effects. Pyrimidines / therapeutic use. Salvage Therapy. Thiazoles / therapeutic use

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  • (PMID = 19885746.001).
  • [ISSN] 1559-131X
  • [Journal-full-title] Medical oncology (Northwood, London, England)
  • [ISO-abbreviation] Med. Oncol.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Benzamides; 0 / Piperazines; 0 / Protein Kinase Inhibitors; 0 / Pyrimidines; 0 / Thiazoles; 8A1O1M485B / Imatinib Mesylate; RBZ1571X5H / Dasatinib
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16. Cony-Makhoul P, Bergeron A, Corm S, Dubruille V, Rea D, Rigal-Huguet F, Nicolini FE: [Guidelines for the management of dasatinib (Sprycel)-induced side effects in chronic myelogenous leukemia and Philadelphia positive acute lymphoblastic leukemias]. Bull Cancer; 2008 Sep;95(9):805-11
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  • [Title] [Guidelines for the management of dasatinib (Sprycel)-induced side effects in chronic myelogenous leukemia and Philadelphia positive acute lymphoblastic leukemias].
  • Dasatinib (Sprycel) is a new-targeted therapy used since 2005 in the treatment of chronic myelogenous leukemia and de novo Philadelphia positive acute lymphoblastic leukaemia patients, intolerant or resistant to imatinib.
  • [MeSH-major] Antineoplastic Agents / adverse effects. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy. Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy. Pyrimidines / adverse effects. Thiazoles / adverse effects

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  • (PMID = 18829412.001).
  • [ISSN] 1769-6917
  • [Journal-full-title] Bulletin du cancer
  • [ISO-abbreviation] Bull Cancer
  • [Language] fre
  • [Publication-type] English Abstract; Journal Article; Practice Guideline
  • [Publication-country] France
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Benzamides; 0 / Piperazines; 0 / Pyrimidines; 0 / Thiazoles; 8A1O1M485B / Imatinib Mesylate; RBZ1571X5H / Dasatinib
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17. Li Q, Chen Z, You Y, Zou P: Transient pancytopenia preceding acute lymphoblastic leukemia with positive Philadelphia chromosome. Leuk Res; 2008 Aug;32(8):1317-20
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  • [Title] Transient pancytopenia preceding acute lymphoblastic leukemia with positive Philadelphia chromosome.
  • Transient pancytopenia preceding acute lymphoblastic leukemia (pre-ALL) is a rare but well-known occurrence usually affecting children and adolescents.
  • Though pre-ALL in a few adults has ever been reported, the association of this preleukemic syndrome with positive Philadelphia chromosome and P190(BCR-ABL) is extremely rare.
  • To the best of our knowledge, this is the first report of adult B-cell type pre-ALL with positive Philadelphia chromosome and P190(BCR-ABL) published in the literature.
  • We report the case of a 49-year-old woman who was diagnosed with B-cell type ALL associated positive Philadelphia chromosome and P190(BCR-ABL) preceded by transient pancytopenia.
  • [MeSH-minor] Female. Fusion Proteins, bcr-abl / analysis. Humans. Immunophenotyping. Middle Aged. Precursor Cell Lymphoblastic Leukemia-Lymphoma. Preleukemia / diagnosis

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  • (PMID = 18291524.001).
  • [ISSN] 0145-2126
  • [Journal-full-title] Leukemia research
  • [ISO-abbreviation] Leuk. Res.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] EC 2.7.10.2 / Fusion Proteins, bcr-abl
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18. Thörn I, Botling J, Hermansson M, Lönnerholm G, Sundström C, Rosenquist R, Barbany G: Monitoring minimal residual disease with flow cytometry, antigen-receptor gene rearrangements and fusion transcript quantification in Philadelphia-positive childhood acute lymphoblastic leukemia. Leuk Res; 2009 Aug;33(8):1047-54
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  • [Title] Monitoring minimal residual disease with flow cytometry, antigen-receptor gene rearrangements and fusion transcript quantification in Philadelphia-positive childhood acute lymphoblastic leukemia.
  • In this study, we followed minimal residual disease (MRD) in eight children with Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL) using (i) flow cytometry (FCM), (ii) real-time quantitative PCR of IG/TCR gene rearrangements and (iii) RT-PCR detecting fusion gene transcripts.
  • The other discordant case showed high BCR-ABL1 RNA level while the other methods did not detect any MRD.
  • However, BCR-ABL1 expression may not reflect the percentage of leukemic cells as FCM and IG/TCR rearrangement quantification do, and these methods are thus complementary.
  • [MeSH-major] Flow Cytometry / methods. Gene Expression Regulation, Leukemic. Gene Rearrangement, T-Lymphocyte. Precursor Cell Lymphoblastic Leukemia-Lymphoma / metabolism. Proto-Oncogene Proteins c-abl / biosynthesis. RNA, Messenger / biosynthesis. RNA, Neoplasm / biosynthesis. Reverse Transcriptase Polymerase Chain Reaction / methods
  • [MeSH-minor] Adolescent. Child. Child, Preschool. Female. Humans. Male. Monitoring, Physiologic / methods. Neoplasm, Residual. Philadelphia Chromosome. Predictive Value of Tests

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  • (PMID = 19157547.001).
  • [ISSN] 1873-5835
  • [Journal-full-title] Leukemia research
  • [ISO-abbreviation] Leuk. Res.
  • [Language] eng
  • [Publication-type] Comparative Study; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / RNA, Messenger; 0 / RNA, Neoplasm; EC 2.7.10.2 / Proto-Oncogene Proteins c-abl
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19. Nishioka C, Ikezoe T, Yang J, Yokoyama A: Long-term exposure of leukemia cells to multi-targeted tyrosine kinase inhibitor induces activations of AKT, ERK and STAT5 signaling via epigenetic silencing of the PTEN gene. Leukemia; 2010 Sep;24(9):1631-40
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  • [Title] Long-term exposure of leukemia cells to multi-targeted tyrosine kinase inhibitor induces activations of AKT, ERK and STAT5 signaling via epigenetic silencing of the PTEN gene.
  • Imatinib induces complete molecular response in patients with chronic myeloid leukemia (CML) and chronic eosinophilic leukemia (CEL).
  • Notably, hypermethylation of the promoter region of the PTEN gene in association with the downregulation of this gene's transcripts was identified in imatinib-resistant leukemia cells isolated from individuals with CEL, CML and Philadelphia-positive acute lymphoblastic leukemia.
  • Taken together, epigenetic silence of PTEN is one of the mechanisms that cause drug resistance in individuals with leukemia after exposure to imatinib.
  • [MeSH-major] Epigenesis, Genetic. Extracellular Signal-Regulated MAP Kinases / metabolism. Gene Silencing. Hypereosinophilic Syndrome / pathology. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology. PTEN Phosphohydrolase / genetics. Protein Kinase Inhibitors / pharmacology. Proto-Oncogene Proteins c-akt / metabolism. STAT5 Transcription Factor / metabolism. Signal Transduction
  • [MeSH-minor] Base Sequence. Blotting, Western. Cell Cycle / drug effects. Cell Line, Tumor. Chromatin Immunoprecipitation. DNA Primers. Enzyme Activation. Flow Cytometry. Humans. Reverse Transcriptase Polymerase Chain Reaction

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  • (PMID = 20596030.001).
  • [ISSN] 1476-5551
  • [Journal-full-title] Leukemia
  • [ISO-abbreviation] Leukemia
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 0 / DNA Primers; 0 / Protein Kinase Inhibitors; 0 / STAT5 Transcription Factor; EC 2.7.11.1 / Proto-Oncogene Proteins c-akt; EC 2.7.11.24 / Extracellular Signal-Regulated MAP Kinases; EC 3.1.3.48 / PTEN protein, human; EC 3.1.3.67 / PTEN Phosphohydrolase
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20. Tonyali O, Coskun U, Yildiz R, Karakan T, Demirci U, Akyurek N, Benekli M, Buyukberber S: Imatinib mesylate-induced acute liver failure in a patient with gastrointestinal stromal tumors. Med Oncol; 2010 Sep;27(3):768-73
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  • [Title] Imatinib mesylate-induced acute liver failure in a patient with gastrointestinal stromal tumors.
  • Imatinib mesylate is a drug that has been approved for treatment of chronic myeloid leukemia, Philadelphia-positive acute lymphoblastic leukemia, and advanced gastrointestinal stromal tumors.
  • We report a 53-year-old woman with advanced gastrointestinal stromal tumors who developed hepatotoxicity while receiving imatinib and subsequently acute liver failure.
  • In cases of imatinib-induced acute hepatitis, the administration of prednisolone may be useful in the resolution of the acute episode and allow the reintroduction of a drug without risking recurrence of hepatitis.
  • [MeSH-minor] Acute Disease. Anti-Inflammatory Agents / therapeutic use. Benzamides. Female. Humans. Imatinib Mesylate. Indoles / therapeutic use. Liver / pathology. Middle Aged. Peritoneal Neoplasms / drug therapy. Peritoneal Neoplasms / secondary. Prednisolone / therapeutic use. Pyrroles / therapeutic use

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  • (PMID = 19662540.001).
  • [ISSN] 1559-131X
  • [Journal-full-title] Medical oncology (Northwood, London, England)
  • [ISO-abbreviation] Med. Oncol.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Anti-Inflammatory Agents; 0 / Antineoplastic Agents; 0 / Benzamides; 0 / Indoles; 0 / Piperazines; 0 / Protein Kinase Inhibitors; 0 / Pyrimidines; 0 / Pyrroles; 0 / sunitinib; 8A1O1M485B / Imatinib Mesylate; 9PHQ9Y1OLM / Prednisolone
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21. Mullighan CG, Zhang J, Harvey RC, Collins-Underwood JR, Schulman BA, Phillips LA, Tasian SK, Loh ML, Su X, Liu W, Devidas M, Atlas SR, Chen IM, Clifford RJ, Gerhard DS, Carroll WL, Reaman GH, Smith M, Downing JR, Hunger SP, Willman CL: JAK mutations in high-risk childhood acute lymphoblastic leukemia. Proc Natl Acad Sci U S A; 2009 Jun 9;106(23):9414-8
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  • [Title] JAK mutations in high-risk childhood acute lymphoblastic leukemia.
  • Pediatric acute lymphoblastic leukemia (ALL) is a heterogeneous disease consisting of distinct clinical and biological subtypes that are characterized by specific chromosomal abnormalities or gene mutations.
  • Mutation of genes encoding tyrosine kinases is uncommon in ALL, with the exception of Philadelphia chromosome-positive ALL, where the t(9,22)(q34;q11) translocation encodes the constitutively active BCR-ABL1 tyrosine kinase.
  • We recently identified a poor prognostic subgroup of pediatric BCR-ABL1-negative ALL patients characterized by deletion of IKZF1 (encoding the lymphoid transcription factor IKAROS) and a gene expression signature similar to BCR-ABL1-positive ALL, raising the possibility of activated tyrosine kinase signaling within this leukemia subtype.
  • Here, we report activating mutations in the Janus kinases JAK1 (n = 3), JAK2 (n = 16), and JAK3 (n = 1) in 20 (10.7%) of 187 BCR-ABL1-negative, high-risk pediatric ALL cases.
  • The JAK-mutated cases had a gene expression signature similar to BCR-ABL1 pediatric ALL, and they had a poor outcome.

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  • (PMID = 19470474.001).
  • [ISSN] 1091-6490
  • [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 / P30 CA118100; United States / NCI NIH HHS / CA / U10 CA98413; United States / NCI NIH HHS / CA / L40 CA142226; United States / NCI NIH HHS / CA / U01 CA114762; United States / NCI NIH HHS / CA / CA114762; United States / NCI NIH HHS / CA / U10 CA098413; United States / PHS HHS / / N01-C0-12400; United States / NCI NIH HHS / CA / CA098543; United States / Howard Hughes Medical Institute / / ; United States / NICHD NIH HHS / HD / T32 HD044331; United States / NCI NIH HHS / CA / U10 CA098543; United States / NCI NIH HHS / CA / T32 CA128583; United States / NCI NIH HHS / CA / U10 CA98543
  • [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 / IKZF1 protein, human; 148971-36-2 / Ikaros Transcription Factor; EC 2.7.10.2 / Janus Kinase 1; EC 2.7.10.2 / Janus Kinase 3; EC 2.7.10.2 / Janus Kinases
  • [Other-IDs] NLM/ PMC2695045
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22. Khalil SH: Molecular hematology. Qualitative to quantitative techniques. Saudi Med J; 2005 Oct;26(10):1516-22
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  • The Section of Hematology, Department of Pathology and Laboratory Medicine at King Faisal Specialist Hospital and Research Center has shared this experience during the last 10 years with more than 6,546 samples submitted for the analysis of different gene rearrangements, fusion gene transcripts and gene mutations including Ig heavy chain gene rearrangement for B-cell malignancies, T-cell receptor gamma chain gene rearrangement for T-cell malignancies, BCR/ABL-P210 and P190 fusion gene transcripts, for chronic myeloid leukemia and Philadelphia positive acute lymphoblastic leukemia, PML/RARalpha fusion gene for promyelocytic leukemia, AML1/ETO for acute myeloid leukemia AML-M2 with t8;21, CBFB/MYH11 for AML M4E0 with inv 16, BCL-2 for follicular lymphoma, and BCL-1 for mantle cell lymphoma.
  • Hence, most molecular assays are qualitative in nature, quantitative assays are deemed necessary in the monitoring and follow-up of minimal residual disease in leukemia and lymphoma, and proved in our experience to serve as an essential tool to confirm complete remission CR post-chemotherapy and bone marrow transplantation, and to detect signs of early relapse for proper clinical intervention.

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  • (PMID = 16228048.001).
  • [ISSN] 0379-5284
  • [Journal-full-title] Saudi medical journal
  • [ISO-abbreviation] Saudi Med J
  • [Language] eng
  • [Publication-type] Comparative Study; Journal Article; Review
  • [Publication-country] Saudi Arabia
  • [Number-of-references] 36
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23. Kim SJ, Park TS, Lee ST, Song J, Suh B, Kim SH, Jang SJ, Lee CH, Choi JR: Therapy-related myelodysplastic syndrome/acute myeloid leukemia after treatment with temozolomide in a patient with glioblastoma multiforme. Ann Clin Lab Sci; 2009;39(4):392-8
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  • [Title] Therapy-related myelodysplastic syndrome/acute myeloid leukemia after treatment with temozolomide in a patient with glioblastoma multiforme.
  • Therapy-related myelodysplastic syndrome and acute leukemia after treatment with temozolomide have rarely been described in the literature.
  • The cases included anaplastic astrocytoma (4 cases), anaplastic oligodendroglioma (2 cases), low grade astrocytoma (2 cases), low grade oligodendroglioma (1 case), and one case of secondary Philadelphia-positive acute lymphoblastic leukemia in a patient with glioblastoma multiforme.
  • Here we report a novel case of therapy-related myelodysplastic syndrome/acute myeloid leukemia associated with der(1;7)(q10;p10) in a glioblastoma multiforme patient treated with temozolomide.
  • In past reports, karyotypes in cases of therapy-related myelodysplastic syndrome/acute myeloid leukemia mostly demonstrated abnormalities in chromosomes 5 and 7.
  • However, we report a case of temozolomide-related myelodysplastic syndrome/acute myeloid leukemia with der(1;7)(q10;p10), possibly the first reported case, to the authors' knowledge.
  • [MeSH-major] Dacarbazine / analogs & derivatives. Glioblastoma / drug therapy. Leukemia, Myeloid, Acute / chemically induced. Myelodysplastic Syndromes / chemically induced


24. Dai G, Pfister M, Blackwood-Chirchir A, Roy A: Importance of characterizing determinants of variability in exposure: application to dasatinib in subjects with chronic myeloid leukemia. J Clin Pharmacol; 2008 Nov;48(11):1254-69
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  • [Title] Importance of characterizing determinants of variability in exposure: application to dasatinib in subjects with chronic myeloid leukemia.
  • The main aims of this model-based analysis were (1) to characterize the IOV and IIV of dasatinib, a novel, orally administered, multitargeted kinase inhibitor of BCR-ABL and SRC family kinases that is indicated for the treatment of chronic myeloid leukemia and Philadelphia-positive acute lymphoblastic leukemia and (2) to demonstrate using simulated data that it is possible to estimate IIV and IOV in relative bioavailability (F(R)) of an orally administered drug, given an adequate sampling scheme.
  • [MeSH-major] Antineoplastic Agents / pharmacokinetics. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy. Models, Biological. Protein Kinase Inhibitors / pharmacokinetics. Pyrimidines / pharmacokinetics. Thiazoles / pharmacokinetics


25. Fujimaki K, Tanaka M, Takasaki H, Hyo R, Kawano T, Sakai R, Fujita H, Fujisawa S, Kanamori H, Maruta A, Ishigatsubo Y: Thiotepa/cyclophosphamide/TBI as a conditioning regimen for allogeneic hematopoietic stem cell transplantation in patients aged 50 years and over. Intern Med; 2008;47(5):379-83
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  • [Title] Thiotepa/cyclophosphamide/TBI as a conditioning regimen for allogeneic hematopoietic stem cell transplantation in patients aged 50 years and over.
  • OBJECTIVE: To reduce the relapse rate for hematological malignancies after allogeneic hematopoietic stem cell transplantation, we employed a myeloablative regimen comprising thiotepa 400 mg/m(2), cyclophosphamide 3,600 mg/m(2) and total body irradiation 10 Gy.
  • MATERIALS AND METHODS: Subjects comprised 17 patients (median age, 53 years; range, 50-56 years) with hematological malignancies who received allogeneic hematopoietic stem cell transplantation from HLA-identical related (n=6), HLA-mismatched family (n=2) or unrelated donors (n=9).
  • Prophylaxis of acute graft-versus-host disease (GVHD) consisted of short-term methotrexate and cyclosporine (n=4) or short-term methotrexate and tacrolimus (n=13).
  • Acute grade II-IV GVHD developed in 7 patients, with chronic GVHD in 11 patients.
  • Only 1 patient with Philadelphia-positive acute lymphoblastic leukemia experienced relapse.
  • [MeSH-major] Antineoplastic Agents, Alkylating / administration & dosage. Cyclophosphamide / administration & dosage. Hematopoietic Stem Cell Transplantation / methods. Thiotepa / administration & dosage. Transplantation Conditioning / methods. Whole-Body Irradiation

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  • (PMID = 18310967.001).
  • [ISSN] 1349-7235
  • [Journal-full-title] Internal medicine (Tokyo, Japan)
  • [ISO-abbreviation] Intern. Med.
  • [Language] eng
  • [Publication-type] Clinical Trial; Journal Article
  • [Publication-country] Japan
  • [Chemical-registry-number] 0 / Antineoplastic Agents, Alkylating; 8N3DW7272P / Cyclophosphamide; 905Z5W3GKH / Thiotepa
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26. Harrison CJ, Haas O, Harbott J, Biondi A, Stanulla M, Trka J, Izraeli S, Biology and Diagnosis Committee of International Berlin-Frankfürt-Münster study group: Detection of prognostically relevant genetic abnormalities in childhood B-cell precursor acute lymphoblastic leukaemia: recommendations from the Biology and Diagnosis Committee of the International Berlin-Frankfürt-Münster study group. Br J Haematol; 2010 Oct;151(2):132-42
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  • [Title] Detection of prognostically relevant genetic abnormalities in childhood B-cell precursor acute lymphoblastic leukaemia: recommendations from the Biology and Diagnosis Committee of the International Berlin-Frankfürt-Münster study group.
  • Treatment of childhood acute lymphoblastic leukaemia (ALL) has improved considerably in recent years.
  • Here we review the current diagnostic criteria of genetic abnormalities in precursor B-ALL (BCP-ALL), including the relevant technical approaches and the application of the most appropriate methods for the detection of each abnormality.
  • The abnormalities with the most significant impact for treatment and management of BCP-ALL are t(9;22)(q34;q11)/BCR-ABL1, t(4;11)(q21;q23)/MLL-AFF1 and near-haploidy/low hypodiploidy for high risk stratification and, to a lesser extent, t(12;21)(p13;q22)/ETV6-RUNX1 and high hyperdiploidy for good risk management.
  • [MeSH-major] Chromosome Aberrations. Leukemia, B-Cell / genetics. Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics

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  • [Copyright] © 2010 Blackwell Publishing Ltd.
  • (PMID = 20701601.001).
  • [ISSN] 1365-2141
  • [Journal-full-title] British journal of haematology
  • [ISO-abbreviation] Br. J. Haematol.
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] England
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27. Pfeifer H, Wassmann B, Pavlova A, Wunderle L, Oldenburg J, Binckebanck A, Lange T, Hochhaus A, Wystub S, Brück P, Hoelzer D, Ottmann OG: Kinase domain mutations of BCR-ABL frequently precede imatinib-based therapy and give rise to relapse in patients with de novo Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL). Blood; 2007 Jul 15;110(2):727-34
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  • [Title] Kinase domain mutations of BCR-ABL frequently precede imatinib-based therapy and give rise to relapse in patients with de novo Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL).
  • Acquired imatinib resistance in advanced Philadelphia-positive acute lymphoblastic leukemia (Ph(+) ALL) has been associated with mutations in the kinase domain (KD) of BCR-ABL.
  • Patients enrolled in the German Multicenter Study Group for Adult Acute Lymphoblastic Leukemia (GMALL) trial ADE10 for newly diagnosed elderly Ph(+) ALL were retrospectively examined for the presence of BCR-ABL KD mutations by denaturing high-performance liquid chromatography (D-HPLC), cDNA sequencing, and allele-specific polymerase chain reaction (PCR).
  • At relapse, the dominant cell clone harbored an identical mutation in 90% of cases, the overall prevalence of mutations at relapse was 80%.
  • P-loop mutations predominated and were not associated with an inferior hematologic or molecular remission rate or shorter remission duration compared with unmutated BCR-ABL.
  • BCR-ABL mutations conferring high-level imatinib resistance are present in a substantial proportion of patients with de novo Ph(+) ALL and eventually give rise to relapse.
  • This provides a rationale for the frontline use of kinase inhibitors active against these BCR-ABL mutants.
  • [MeSH-major] Fusion Proteins, bcr-abl / genetics. Mutation. Piperazines / therapeutic use. Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy. Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics. Pyrimidines / therapeutic use

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  • (PMID = 17405907.001).
  • [ISSN] 0006-4971
  • [Journal-full-title] Blood
  • [ISO-abbreviation] Blood
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [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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28. IMAHASHI N, TOKUNAGA M, NISHIWAKI S, YANAGISAWA M, OZAWA Y, MIYAMURA K: Successful treatment with imatinib-combined chemotherapy for relapsed Philadelphia-positive acute lymphoblastic leukemia after allogeneic bone marrow transplantation. Rinsho Ketsueki; 2009 Nov;50(11):1612-5
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  • [Title] Successful treatment with imatinib-combined chemotherapy for relapsed Philadelphia-positive acute lymphoblastic leukemia after allogeneic bone marrow transplantation.
  • The prognosis of patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+)ALL) relapsing after allogeneic hematopoietic stem cell transplantation is dismal.
  • Our case suggests that by continuing imatinib after the induction of molecular remission by imatinib-combined chemotherapy, the antileukemic activity of imatinib could achieve durable remission in combination with the graft-versus-leukemia effect.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Bone Marrow Transplantation. Hematopoietic Stem Cell Transplantation. Neoplasm Recurrence, Local. Piperazines / administration & dosage. Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy. Pyrimidines / administration & dosage
  • [MeSH-minor] Benzamides. Disease-Free Survival. Drug Administration Schedule. Female. Graft vs Leukemia Effect. Humans. Imatinib Mesylate. Middle Aged. Remission Induction. Transplantation, Homologous. Treatment Outcome

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  • (PMID = 20009435.001).
  • [ISSN] 0485-1439
  • [Journal-full-title] [Rinshō ketsueki] The Japanese journal of clinical hematology
  • [ISO-abbreviation] Rinsho Ketsueki
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] Japan
  • [Chemical-registry-number] 0 / Benzamides; 0 / Piperazines; 0 / Pyrimidines; 8A1O1M485B / Imatinib Mesylate
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29. Chevallier P, Mahe B, Garand R, Talmant P, Harousseau JL, Delaunay J: Combination of chemotherapy and gemtuzumab ozogamicin in adult Philadelphia positive acute lymphoblastic leukemia patient harboring CD33 expression. Int J Hematol; 2008 Sep;88(2):209-11
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Combination of chemotherapy and gemtuzumab ozogamicin in adult Philadelphia positive acute lymphoblastic leukemia patient harboring CD33 expression.
  • It was developed at the end of the nineties as 90% of the leukemic blast population of patients with acute myeloid leukaemia (AML) express the CD33 surface antigen (Dinndorf et al. [1] Blood 1986;67:1048-53).
  • CD33 antigen expression is also observed at diagnosis (in 15% of cases) (Pui et al. [3] J Clin Oncol 1998;16:3768-73) or at relapse (Guglielmi et al. [4] Leukemia 1997; 11:1501-7) of acute lymphoblastic leukaemia (ALL), representing a potential cellular target for ALL patients.
  • Case series have already demonstrated the efficacy of GO in children with relapsed CD33+ ALL with documentation of complete remission (CR) (Balduzzi et al. [5] Leukemia 2003;17:2247-8; Cotter et al. [6] Br J Haematol 2003;122:686-91; Zwaan et al. [7] Leukemia 2003;17:468-70).
  • [MeSH-major] Aminoglycosides / administration & dosage. Antibodies, Monoclonal / administration & dosage. Antineoplastic Agents / administration & dosage. Philadelphia Chromosome. Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy. Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics
  • [MeSH-minor] Adult. Antibodies, Monoclonal, Humanized. Antigens, CD / metabolism. Antigens, Differentiation, Myelomonocytic / metabolism. Antineoplastic Combined Chemotherapy Protocols / administration & dosage. Combined Modality Therapy. Fatal Outcome. Hematopoietic Stem Cell Transplantation. Humans. Male. Remission Induction. Sialic Acid Binding Ig-like Lectin 3

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  • (PMID = 18668307.001).
  • [ISSN] 0925-5710
  • [Journal-full-title] International journal of hematology
  • [ISO-abbreviation] Int. J. Hematol.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Aminoglycosides; 0 / Antibodies, Monoclonal; 0 / Antibodies, Monoclonal, Humanized; 0 / Antigens, CD; 0 / Antigens, Differentiation, Myelomonocytic; 0 / Antineoplastic Agents; 0 / CD33 protein, human; 0 / Sialic Acid Binding Ig-like Lectin 3; 0 / gemtuzumab
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30. Wassmann B, Pfeifer H, Stadler M, Bornhaüser M, Bug G, Scheuring UJ, Brück P, Stelljes M, Schwerdtfeger R, Basara N, Perz J, Bunjes D, Ledderose G, Mahlberg R, Binckebanck A, Gschaidmeier H, Hoelzer D, Ottmann OG: Early molecular response to posttransplantation imatinib determines outcome in MRD+ Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL). Blood; 2005 Jul 15;106(2):458-63
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  • [Title] Early molecular response to posttransplantation imatinib determines outcome in MRD+ Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL).
  • In adult Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL), minimal residual disease (MRD) after stem cell transplantation (SCT) is associated with a relapse probability exceeding 90%.
  • Bcr-abl transcripts became undetectable in 14 (52%) of 27 patients, after a median of 1.5 months (0.9-3.7 months) ((early)CR(mol)).
  • Continued detection of bcr-abl transcripts after 2 to 3 months on imatinib identifies patients who will ultimately experience relapse and in whom additional or alternative antileukemic treatment should be initiated.
  • [MeSH-major] Antineoplastic Agents / therapeutic use. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy. Piperazines / therapeutic use. Pyrimidines / therapeutic use
  • [MeSH-minor] Adolescent. Adult. Benzamides. Female. Genes, abl. Hematopoietic Stem Cell Transplantation. Humans. Imatinib Mesylate. Male. Middle Aged. Prospective Studies. Recurrence. Treatment Outcome


31. Pane F, Cimino G, Izzo B, Camera A, Vitale A, Quintarelli C, Picardi M, Specchia G, Mancini M, Cuneo A, Mecucci C, Martinelli G, Saglio G, Rotoli B, Mandelli F, Salvatore F, Foà R, GIMEMA group: Significant reduction of the hybrid BCR/ABL transcripts after induction and consolidation therapy is a powerful predictor of treatment response in adult Philadelphia-positive acute lymphoblastic leukemia. Leukemia; 2005 Apr;19(4):628-35
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  • [Title] Significant reduction of the hybrid BCR/ABL transcripts after induction and consolidation therapy is a powerful predictor of treatment response in adult Philadelphia-positive acute lymphoblastic leukemia.
  • Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) has a dismal prognosis.
  • We prospectively evaluated minimal residual disease (MRD) by measuring BCR/ ABL levels with a quantitative real-time PCR procedure after induction and after consolidation in 45 adults with Ph+ ALL who obtained complete hematological remission after a high-dose daunorubicin induction schedule.
  • At diagnosis, the mean BCR-ABL/GUS ratio was 1.55 +/- 1.78.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Fusion Proteins, bcr-abl / genetics. Philadelphia Chromosome. Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy. Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics

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  • (PMID = 15744351.001).
  • [ISSN] 0887-6924
  • [Journal-full-title] Leukemia
  • [ISO-abbreviation] Leukemia
  • [Language] eng
  • [Publication-type] Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antibiotics, Antineoplastic; 0 / Antimetabolites, Antineoplastic; 0 / Antineoplastic Agents, Phytogenic; 04079A1RDZ / Cytarabine; 5J49Q6B70F / Vincristine; EC 2.7.10.2 / Fusion Proteins, bcr-abl; EC 3.5.1.1 / Asparaginase; ZS7284E0ZP / Daunorubicin
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32. Takashima S, Numata A, Miyamoto T, Shirakawa T, Kinoshita R, Kato K, Takenaka K, Harada N, Nagafuji K, Taniguchi S, Harada M: [Acute lymphoblastic leukemia presenting with calcineurin-inhibitor induced pain syndrome after a second allogeneic bone marrow transplantation]. Rinsho Ketsueki; 2006 Oct;47(10):1372-6
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  • [Title] [Acute lymphoblastic leukemia presenting with calcineurin-inhibitor induced pain syndrome after a second allogeneic bone marrow transplantation].
  • A 42-year-old woman was referred to us for the treatment of relapsed Philadelphia-positive acute lymphoblastic leukemia (Ph+ALL), which had been maintained in complete remission for seven years after an allogeneic bone marrow transplantation (allo-BMT) from an unrelated donor.
  • CIPS is rarely seen following allogeneic stem cell transplantation (allo-SCT); only three cases have been so far reported to our knowledge.
  • [MeSH-major] Bone Marrow Transplantation. Calcineurin / adverse effects. Calcineurin Inhibitors. Complex Regional Pain Syndromes / chemically induced. Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy
  • [MeSH-minor] Adult. Female. Hematopoietic Stem Cell Transplantation. Humans. Transplantation Conditioning

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  • (PMID = 17094576.001).
  • [ISSN] 0485-1439
  • [Journal-full-title] [Rinshō ketsueki] The Japanese journal of clinical hematology
  • [ISO-abbreviation] Rinsho Ketsueki
  • [Language] jpn
  • [Publication-type] Case Reports; English Abstract; Journal Article
  • [Publication-country] Japan
  • [Chemical-registry-number] 0 / Calcineurin Inhibitors; EC 3.1.3.16 / Calcineurin
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33. Klyuchnikov E, Schafhausen P, Kröger N, Brummendorf TH, Osanmaz O, Asenova S, Zabelina T, Ocheni S, Ayuk F, Zander AR, Bacher U: Second-generation tyrosine kinase inhibitors in the post-transplant period in patients with chronic myeloid leukemia or Philadelphia-positive acute lymphoblastic leukemia. Acta Haematol; 2009;122(1):6-10
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Second-generation tyrosine kinase inhibitors in the post-transplant period in patients with chronic myeloid leukemia or Philadelphia-positive acute lymphoblastic leukemia.
  • [MeSH-major] Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy. Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy. Protein Kinase Inhibitors / therapeutic use. Protein-Tyrosine Kinases / antagonists & inhibitors
  • [MeSH-minor] Aged. Aniline Compounds / therapeutic use. Benzamides. Dasatinib. Female. Humans. Imatinib Mesylate. Male. Middle Aged. Nitriles / therapeutic use. Piperazines / therapeutic use. Pyrimidines / therapeutic use. Quinolines / therapeutic use. Stem Cell Transplantation. Thiazoles / therapeutic use

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  • (PMID = 19602874.001).
  • [ISSN] 1421-9662
  • [Journal-full-title] Acta haematologica
  • [ISO-abbreviation] Acta Haematol.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] Switzerland
  • [Chemical-registry-number] 0 / 4-methyl-N-(3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl)-3-((4-pyridin-3-ylpyrimidin-2-yl)amino)benzamide; 0 / Aniline Compounds; 0 / Benzamides; 0 / Nitriles; 0 / Piperazines; 0 / Protein Kinase Inhibitors; 0 / Pyrimidines; 0 / Quinolines; 0 / Thiazoles; 5018V4AEZ0 / bosutinib; 8A1O1M485B / Imatinib Mesylate; EC 2.7.10.1 / Protein-Tyrosine Kinases; RBZ1571X5H / Dasatinib
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34. Shimoni A, Leiba M, Schleuning M, Martineau G, Renaud M, Koren-Michowitz M, Ribakovski E, le Coutre P, Arnold R, Guilhot F, Nagler A: Prior treatment with the tyrosine kinase inhibitors dasatinib and nilotinib allows stem cell transplantation (SCT) in a less advanced disease phase and does not increase SCT Toxicity in patients with chronic myelogenous leukemia and philadelphia positive acute lymphoblastic leukemia. Leukemia; 2009 Jan;23(1):190-4
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  • [Title] Prior treatment with the tyrosine kinase inhibitors dasatinib and nilotinib allows stem cell transplantation (SCT) in a less advanced disease phase and does not increase SCT Toxicity in patients with chronic myelogenous leukemia and philadelphia positive acute lymphoblastic leukemia.
  • [MeSH-major] Hematopoietic Stem Cell Transplantation / methods. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / therapy. Pyrimidines / administration & dosage. Thiazoles / administration & dosage

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  • (PMID = 18596746.001).
  • [ISSN] 1476-5551
  • [Journal-full-title] Leukemia
  • [ISO-abbreviation] Leukemia
  • [Language] eng
  • [Publication-type] Letter
  • [Publication-country] England
  • [Chemical-registry-number] 0 / 4-methyl-N-(3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl)-3-((4-pyridin-3-ylpyrimidin-2-yl)amino)benzamide; 0 / Protein Kinase Inhibitors; 0 / Pyrimidines; 0 / Thiazoles; RBZ1571X5H / Dasatinib
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