Genomic characterization of Imatinib resistance in CD34+ cell populations from chronic myeloid leukaemia patients.
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.
Joha
Sami
S
Institut de Recherche sur le Cancer de Lille (IRCL), Centre JP Aubert, Unité Inserm 837, Lille, France. samijoha@yahoo.fr
Dauphin
Véronique
V
Leprêtre
Frédéric
F
Corm
Sélim
S
Nicolini
Franck E
FE
Roumier
Christophe
C
Nibourel
Olivier
O
Grardel
Nathalie
N
Maguer-Satta
Véronique
V
Idziorek
Thierry
T
Figeac
Martin
M
Laï
Jean-Luc
JL
Quesnel
Bruno
B
Etienne
Gabriel
G
Guilhot
François
F
Lippert
Eric
E
Preudhomme
Claude
C
Roche-Lestienne
Catherine
C
D018952:Antigens, CD34 / Q000378:metabolism; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001549:Benzamides; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D055028:Comparative Genomic Hybridization; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D018628:Gene Dosage; D016313:Genes, abl / Q000235:genetics; D055106:Genome-Wide Association Study; D006801:Humans; D051740:Ikaros Transcription Factor / Q000235:genetics; D000068877:Imatinib Mesylate; D017404:In Situ Hybridization, Fluorescence; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D010879:Piperazines / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000378:metabolism
D018952:Antigens, CD34; D000970:Antineoplastic Agents; D001549:Benzamides; C497239:IKZF1 protein, human; D010879:Piperazines; D011743:Pyrimidines; D051740:Ikaros Transcription Factor; D000068877:Imatinib Mesylate