Genomic characterization of Imatinib resistance in CD34+ cell populations from chronic myeloid leukaemia patients

Leuk Res. 2011 Apr;35(4):448-58. doi: 10.1016/j.leukres.2010.07.012. Epub 2010 Aug 3.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD34 / metabolism
  • Antineoplastic Agents / therapeutic use
  • Benzamides
  • Chromosomes, Human, Pair 12 / genetics
  • Chromosomes, Human, Pair 13 / genetics
  • Chromosomes, Human, Pair 7 / genetics
  • Comparative Genomic Hybridization
  • Drug Resistance, Neoplasm / genetics*
  • Gene Dosage
  • Genes, abl / genetics
  • Genome-Wide Association Study
  • Humans
  • Ikaros Transcription Factor / genetics
  • Imatinib Mesylate
  • In Situ Hybridization, Fluorescence
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / metabolism
  • Mutation
  • Piperazines / therapeutic use*
  • Pyrimidines / therapeutic use*
  • T-Lymphocytes / metabolism

Substances

  • Antigens, CD34
  • Antineoplastic Agents
  • Benzamides
  • IKZF1 protein, human
  • Piperazines
  • Pyrimidines
  • Ikaros Transcription Factor
  • Imatinib Mesylate