Abstract
To ascertain genomic alterations associated with Imatinib resistance in chronic myeloid leukaemia, we performed high resolution genomic analysis of CD34(+) cells from 25 Imatinib (IM) resistant and 11 responders CML patients. Using patients' T-cells as reference, we found significant association between number of acquired cryptic copy number alterations (CNA) and disease phase (p=0.036) or loss of IM response for patients diagnosed in chronic phase (CP) (p=0.04). Recurrent cryptic losses were identified on chromosomes 7, 12 and 13. On chromosome 7, recurrent deletions of the IKZF1 locus were detected, for the first time, in 4 patients in CP.
Copyright © 2010 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antigens, CD34 / metabolism
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Antineoplastic Agents / therapeutic use
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Benzamides
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Chromosomes, Human, Pair 12 / genetics
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Chromosomes, Human, Pair 13 / genetics
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Chromosomes, Human, Pair 7 / genetics
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Comparative Genomic Hybridization
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Drug Resistance, Neoplasm / genetics*
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Gene Dosage
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Genes, abl / genetics
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Genome-Wide Association Study
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Humans
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Ikaros Transcription Factor / genetics
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Imatinib Mesylate
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In Situ Hybridization, Fluorescence
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics*
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive / metabolism
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Mutation
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Piperazines / therapeutic use*
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Pyrimidines / therapeutic use*
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T-Lymphocytes / metabolism
Substances
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Antigens, CD34
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Antineoplastic Agents
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Benzamides
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IKZF1 protein, human
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Piperazines
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Pyrimidines
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Ikaros Transcription Factor
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Imatinib Mesylate