High EVI1 expression predicts poor survival in acute myeloid leukemia: a study of 319 de novo AML patients
The proto-oncogene EVI1 encodes a DNA binding protein and is located on chromosome 3q26. The gene is aberrantly expressed in acute myeloid leukemia (AML) patients carrying 3q26 abnormalities. Two mRNAs are transcribed from this locus: EVI1 and a fusion of EVI1 with MDS1 (MDS1-EVI1), a gene located 5' of EVI1. The purpose of this study was to investigate which of the 2 gene products is involved in transformation in human AML. To discriminate between EVI1 and MDS1-EVI1 transcripts, distinct real-time quantitative polymerase chain reaction (PCR) assays were developed. Patients with 3q26 abnormalities often showed high EVI1 and MDS1-EVI1 expression. In a cohort of 319 AML patients, 4 subgroups could be distinguished: EVI1(+) and MDS1-EVI1(-) (6 patients; group I), EVI1(+) and MDS1-EVI1(+) (26 patients; group II), EVI1(-) and MDS1-EVI1(+) (12 patients; group III), and EVI1(-) and MDS1-EVI1(-) (275 patients; group IV). The only 4 patients with a 3q26 aberration belonged to groups I and II. Interestingly, high EVI1 and not MDS1-EVI1 expression was associated with unfavorable karyotypes (eg, -7/7q-) or complex karyotypes. Moreover, a significant correlation was observed between EVI1 expression and 11q23 aberrations (mixed lineage leukemia [MLL] gene involvement). Patients from groups I and II had significantly shorter overall and event-free survival than patients in groups III and IV. Our data demonstrate that high EVI1 expression is an independent poor prognostic marker within the intermediate- risk karyotypic group.
|*Oncogene Proteins, Fusion, *Proto-Oncogenes, *Transcription Factors, Acute Disease, Adolescent, Adult, Aged, Bone Marrow, Case-Control Studies, Chromosome Aberrations, Chromosomes, Human, Pair 3, DNA-Binding Proteins/genetics/*metabolism, Female, Gene Expression, Humans, Leukemia, Myeloid/*metabolism/*mortality/therapy, Male, Middle Aged, Neoplasm Proteins/genetics/metabolism, Polymerase Chain Reaction, Prognosis, RNA, Messenger/analysis, Recombinant Fusion Proteins/genetics/metabolism, Research Support, Non-U.S. Gov't, Survival Analysis, Treatment Outcome|
|Organisation||Erasmus MC: University Medical Center Rotterdam|
Beverloo, H.B, Sonneveld, P, Verhoef, G.E.G, Ossenkoppele, G.J, Delwel, H.R, Verdonck, L.F, … Smit, E.M.E. (2003). High EVI1 expression predicts poor survival in acute myeloid leukemia: a study of 319 de novo AML patients. Blood. Retrieved from http://hdl.handle.net/1765/8228