EVI-1 oncogene expression predicts survival in chronic-phase CML patients resistant to imatinib treated with second-generation tyrosine kinase inhibitors

Autor: Richard E. Clark, Jane F. Apperley, Alistair Reid, Philippa C. May, Mustafa Daghistani, Letizia Foroni, David Marin, Lihui Wang, Jamshid S. Khorashad, Gareth Gerrard, Christos Paliompeis, Dragana Milojkovic, John M. Goldman, Valeria A. S. De Melo
Rok vydání: 2010
Předmět:
Male
Oncology
medicine.medical_specialty
medicine.drug_class
Immunology
Dasatinib
Biochemistry
Piperazines
Tyrosine-kinase inhibitor
hemic and lymphatic diseases
Internal medicine
Proto-Oncogenes
medicine
Humans
RNA
Messenger
RNA
Neoplasm
Protein Kinase Inhibitors
Survival rate
In Situ Hybridization
Fluorescence
Salvage Therapy
Reverse Transcriptase Polymerase Chain Reaction
business.industry
Myeloid leukemia
Imatinib
Cell Biology
Hematology
Middle Aged
Protein-Tyrosine Kinases
Prognosis
medicine.disease
MDS1 and EVI1 Complex Locus Protein
DNA-Binding Proteins
Survival Rate
Thiazoles
Pyrimidines
Imatinib mesylate
Nilotinib
Drug Resistance
Neoplasm
Benzamides
Leukemia
Myeloid
Chronic-Phase
Imatinib Mesylate
Female
Blast Crisis
business
Transcription Factors
Chronic myelogenous leukemia
medicine.drug
Zdroj: Blood. 116:6014-6017
ISSN: 1528-0020
0006-4971
Popis: 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.
Databáze: OpenAIRE
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