title: Genomic characterization of Imatinib resistance in CD34+ cell populations from chronic myeloid leukaemia patients.
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.
authors.affiliation: Institut de Recherche sur le Cancer de Lille (IRCL), Centre JP Aubert, Unité Inserm 837, Lille, France. samijoha@yahoo.fr
authors.forename: Sami
authors.initials: S
authors.lastname: Joha
authors.forename: Véronique
authors.initials: V
authors.lastname: Dauphin
authors.forename: Frédéric
authors.initials: F
authors.lastname: Leprêtre
authors.forename: Sélim
authors.initials: S
authors.lastname: Corm
authors.forename: Franck E
authors.initials: FE
authors.lastname: Nicolini
authors.forename: Christophe
authors.initials: C
authors.lastname: Roumier
authors.forename: Olivier
authors.initials: O
authors.lastname: Nibourel
authors.forename: Nathalie
authors.initials: N
authors.lastname: Grardel
authors.forename: Véronique
authors.initials: V
authors.lastname: Maguer-Satta
authors.forename: Thierry
authors.initials: T
authors.lastname: Idziorek
authors.forename: Martin
authors.initials: M
authors.lastname: Figeac
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Laï
authors.forename: Bruno
authors.initials: B
authors.lastname: Quesnel
authors.forename: Gabriel
authors.initials: G
authors.lastname: Etienne
authors.forename: François
authors.initials: F
authors.lastname: Guilhot
authors.forename: Eric
authors.initials: E
authors.lastname: Lippert
authors.forename: Claude
authors.initials: C
authors.lastname: Preudhomme
authors.forename: Catherine
authors.initials: C
authors.lastname: Roche-Lestienne
mesh_terms: 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
chemical_list: D018952:Antigens, CD34; D000970:Antineoplastic Agents; D001549:Benzamides; C497239:IKZF1 protein, human; D010879:Piperazines; D011743:Pyrimidines; D051740:Ikaros Transcription Factor; D000068877:Imatinib Mesylate