title: A gene expression signature of primary resistance to imatinib in chronic myeloid leukemia.
abstract: Using gene expression profiling we show that the expression of 105-probe sets in mononuclear cells collected from chronic myeloid leukemia (CML) chronic phase (CP) patients with raised leukocyte counts who subsequently achieved complete cytogenetic response after 12 months on imatinib, differed substantially from that of patients who failed to achieve any degree of cytogenetic response. In the non-responder cohort, 9 of the 50 overexpressed genes were involved in DNA repair by homologous recombination, whereas 36 genes, including PTEN, were downregulated. This pattern of altered gene expression in responders and non-responders was validated in another independent dataset. These findings may prove useful for identifying at the time of diagnosis a subset of CP-CML patients who are likely to be resistant to imatinib and require an alternative treatment.
authors.affiliation: Centre de Recherche en Cancérologie de Marseille, Laboratoire d'Oncologie Moléculaire, Institut Paoli-Calmettes and Inserm UMR891, Marseille, France.
authors.forename: Hugues
authors.initials: H
authors.lastname: de Lavallade
authors.forename: Pascal
authors.initials: P
authors.lastname: Finetti
authors.forename: Nadine
authors.initials: N
authors.lastname: Carbuccia
authors.forename: Jamshid S
authors.initials: JS
authors.lastname: Khorashad
authors.forename: Aude
authors.initials: A
authors.lastname: Charbonnier
authors.forename: Letizia
authors.initials: L
authors.lastname: Foroni
authors.forename: Jane F
authors.initials: JF
authors.lastname: Apperley
authors.forename: Norbert
authors.initials: N
authors.lastname: Vey
authors.forename: François
authors.initials: F
authors.lastname: Bertucci
authors.forename: Daniel
authors.initials: D
authors.lastname: Birnbaum
authors.forename: Marie-Joëlle
authors.initials: MJ
authors.lastname: Mozziconacci
mesh_terms: D001549:Benzamides; D020732:Cytogenetic Analysis; D004260:DNA Repair / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects*; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000235:genetics*; D015466:Leukemia, Myeloid, Chronic-Phase / Q000235:genetics; D007958:Leukocyte Count; D051059:PTEN Phosphohydrolase / Q000235:genetics; D010879:Piperazines / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D012074:Remission Induction
chemical_list: D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human