EVI-1 oncogene expression predicts survival in chronic-phase CML patients resistant to imatinib treated with second-generation tyrosine kinase inhibitors.
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.
Daghistani
Mustafa
M
Department of Haematology, Imperial College London, Hammersmith Hospital, London, United Kingdom.
Marin
David
D
Khorashad
Jamshid Sorouri
JS
Wang
Lihui
L
May
Philippa C
PC
Paliompeis
Christos
C
Milojkovic
Dragana
D
De Melo
Valeria A
VA
Gerrard
Gareth
G
Goldman
John M
JM
Apperley
Jane F
JF
Clark
Richard E
RE
Foroni
Letizia
L
Reid
Alistair G
AG
D001549:Benzamides; D001752:Blast Crisis; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D000069439:Dasatinib; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D017404:In Situ Hybridization, Fluorescence; D015466:Leukemia, Myeloid, Chronic-Phase / Q000188:drug therapy / Q000235:genetics / Q000401:mortality*; D000074008:MDS1 and EVI1 Complex Locus Protein; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000627:therapeutic use*; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011519:Proto-Oncogenes / Q000235:genetics*; D011743:Pyrimidines / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016879:Salvage Therapy; D015996:Survival Rate; D013844:Thiazoles / Q000627:therapeutic use*; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
D001549:Benzamides; D004268:DNA-Binding Proteins; D000074008:MDS1 and EVI1 Complex Locus Protein; C063575:MECOM protein, human; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D013844:Thiazoles; D014157:Transcription Factors; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; C498826:nilotinib; D000069439:Dasatinib