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1. 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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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [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


2. O'Dwyer ME, Gatter KM, Loriaux M, Druker BJ, Olson SB, Magenis RE, Lawce H, Mauro MJ, Maziarz RT, Braziel RM: Demonstration of Philadelphia chromosome negative abnormal clones in patients with chronic myelogenous leukemia during major cytogenetic responses induced by imatinib mesylate. Leukemia; 2003 Mar;17(3):481-7
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Demonstration of Philadelphia chromosome negative abnormal clones in patients with chronic myelogenous leukemia during major cytogenetic responses induced by imatinib mesylate.
  • Imatinib mesylate, an Abl-specific kinase inhibitor, produces sustained complete hematologic responses (CHR) and major cytogenetic responses (MCR) in chronic myeloid leukemia (CML) patients, but long-term outcomes in these patients are not yet known.
  • This article reports the identification of clonal abnormalities in cells lacking detectable Philadelphia (Ph) chromosome/BCR-ABL rearrangements from seven patients with chronic- or accelerated-phase CML, who were treated with imatinib.
  • All seven patients were refractory or intolerant to interferon therapy.
  • Six of seven patients demonstrated MCR and one patient, who had a cryptic translocation, achieved low-level positivity (2.5%) for BCR-ABL by fluorescence in situ hybridization.
  • The median duration of imatinib treatment before the identification of cytogenetic abnormalities in BCR-ABL-negative cells was 13 months.
  • The most common cytogenetic abnormality was trisomy 8, documented in three patients.
  • All patients had varying degrees of dysplastic morphologic abnormalities.
  • One patient exhibited increased numbers of marrow blasts, yet consistently demonstrated no Ph-positive metaphases and the absence of morphologic features of CML.
  • The presence of clonal abnormalities in Ph-negative cells of imatinib-treated CML patients with MCR and CHR highlights the importance of routine metaphase cytogenetic testing and long-term follow-up of all imatinib-treated patients.
  • [MeSH-major] Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy. Neoplasm, Residual / genetics. Philadelphia Chromosome. Piperazines / pharmacology. Pyrimidines / pharmacology
  • [MeSH-minor] Adult. Aged. Benzamides. Case-Control Studies. Chromosomes, Human, Pair 8. Clone Cells / drug effects. Clone Cells / metabolism. Clone Cells / pathology. Cytogenetic Analysis. Female. Follow-Up Studies. Humans. Imatinib Mesylate. Male. Middle Aged. Reverse Transcriptase Polymerase Chain Reaction. Trisomy

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  • (PMID = 12646934.001).
  • [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
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3. Markert E, Siebolts U, Odenthal M, Kreuzer KA, Wickenhauser C: High diagnostic value of morphologic examination and molecular analysis of bone marrow biopsies in a case of BCR-ABL+ CML with clusters of blasts. Int J Hematol; 2009 Apr;89(3):294-7
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] High diagnostic value of morphologic examination and molecular analysis of bone marrow biopsies in a case of BCR-ABL+ CML with clusters of blasts.
  • We report a clinical case of chronic myelogenous leukaemia (CML) with regional B-lymphoblastic transformation.
  • Peripheral leukocytosis of 160 x 10(9)/L, splenomegaly and fatigue suggested CML.
  • In peripheral blood and bone marrow smears, white blood cells in all maturation stages and only few blasts were seen and therefore the diagnosis of chronic phase CML was proposed.
  • Cytogenetics performed on peripheral blood cells revealed the characteristic t(9;22)(q34;q11) translocation as solitary abnormality.
  • BCR-ABL FISH analysis demonstrated 31% atypical split signals in the B-lymphoid blasts and in the maturing myeloid cells, furthermore, BCR-ABL fusion transcripts were seen in the RT-PCR assay.
  • Imatinib-based therapy led to temporary regression of peripheral leukocytosis.
  • Bone marrow examination 3 weeks after therapy induction demonstrated considerably reduced cellularity and the proportion of B-lymphoid blasts had decreased to 20% of the nuclear cells.
  • BCR-ABL FISH analysis still presented 21% atypical split signals but levels of BCR-ABL transcripts had significantly fallen indicating a rather favourable prognosis.
  • However, 3 months after diagnosis the patient relapsed and developed an immunodeficiency with soor esophagitis and aspergillus pneumonia.
  • A therapy with dasatinib was not successful and the patient died in consequence of immunodeficiency.
  • This report demonstrates the high diagnostic value of bone marrow biopsy in the evaluation of CML.
  • Besides morphology investigation of diverse methods including RT-PCR and FISH performed on diagnostic bone marrow biopsies are obligatory for ideal monitoring of drug response.
  • [MeSH-major] Bone Marrow / metabolism. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / diagnosis. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / metabolism

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  • (PMID = 19229589.001).
  • [ISSN] 1865-3774
  • [Journal-full-title] International journal of hematology
  • [ISO-abbreviation] Int. J. Hematol.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] Japan
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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. 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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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [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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