Abstract
Activation of the EVI-1 oncogene has been reported in acute myeloid leukemia, chronic myeloid leukemia (CML) in blast crisis, and less commonly, in chronic-phase CML patients. We screened an unselected cohort of 75 chronic-phase CML patients who had failed imatinib for expression of EVI-1 and sought a correlation with subsequent outcome on the second-generation tyrosine kinase inhibitors dasatinib (n = 61) or nilotinib (n = 14). The 8 patients (10.7%) who expressed EVI-1 transcripts detectable by real-time polymerase chain reaction had significantly lower event-free survival, progression-free survival, and overall survival than patients with undetectable transcript. The predictive value of EVI-1 expression was validated in an independent cohort. In a multivariate analysis, EVI-1 expression status and the best cytogenetic response obtained on imatinib were the only independent predictors for overall survival, progression-free survival, and event-free survival. Our data suggest that screening for EVI-1 expression at the time of imatinib failure may predict for response to second-line TKI therapy and consequently aid clinical management.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Benzamides
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Blast Crisis
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DNA-Binding Proteins / genetics*
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DNA-Binding Proteins / metabolism
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Dasatinib
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Drug Resistance, Neoplasm / drug effects*
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Female
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Humans
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Imatinib Mesylate
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In Situ Hybridization, Fluorescence
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Leukemia, Myeloid, Chronic-Phase / drug therapy
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Leukemia, Myeloid, Chronic-Phase / genetics
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Leukemia, Myeloid, Chronic-Phase / mortality*
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MDS1 and EVI1 Complex Locus Protein
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Male
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Middle Aged
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Piperazines / therapeutic use*
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Prognosis
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Protein Kinase Inhibitors / therapeutic use*
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Protein-Tyrosine Kinases / antagonists & inhibitors
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Proto-Oncogenes / genetics*
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Pyrimidines / therapeutic use*
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RNA, Messenger / genetics
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RNA, Neoplasm / genetics
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Reverse Transcriptase Polymerase Chain Reaction
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Salvage Therapy
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Survival Rate
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Thiazoles / therapeutic use*
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Transcription Factors / genetics*
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Transcription Factors / metabolism
Substances
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Benzamides
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DNA-Binding Proteins
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MDS1 and EVI1 Complex Locus Protein
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MECOM protein, human
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Piperazines
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Protein Kinase Inhibitors
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Pyrimidines
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RNA, Messenger
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RNA, Neoplasm
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Thiazoles
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Transcription Factors
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Imatinib Mesylate
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Protein-Tyrosine Kinases
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nilotinib
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Dasatinib