A gene expression signature of primary resistance to imatinib in chronic myeloid leukemia.
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.
de Lavallade
Hugues
H
Centre de Recherche en Cancérologie de Marseille, Laboratoire d'Oncologie Moléculaire, Institut Paoli-Calmettes and Inserm UMR891, Marseille, France.
Finetti
Pascal
P
Carbuccia
Nadine
N
Khorashad
Jamshid S
JS
Charbonnier
Aude
A
Foroni
Letizia
L
Apperley
Jane F
JF
Vey
Norbert
N
Bertucci
François
F
Birnbaum
Daniel
D
Mozziconacci
Marie-Joëlle
MJ
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
D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human