High EVI1 expression predicts poor survival in acute myeloid leukemia: a study of 319 de novo AML patients
January 2003
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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.
- Male
- Adult
- Aged
- Female
- Humans
- Research Support, Non-U.S. Gov't
- Recombinant Fusion Proteins/genetics/metabolism
- Acute Disease
- Middle Aged
- Survival Analysis
- Treatment Outcome
- Adolescent
- Prognosis
- Gene Expression
- DNA-Binding Proteins/genetics/*metabolism
- Case-Control Studies
- RNA, Messenger/analysis
- Polymerase Chain Reaction
- Chromosome Aberrations
- Neoplasm Proteins/genetics/metabolism
- *Proto-Oncogenes
- *Transcription Factors
- *Oncogene Proteins, Fusion
- Bone Marrow
- Chromosomes, Human, Pair 3
- Leukemia, Myeloid/*metabolism/*mortality/therapy
- evi 1
- patient
- expression
- evi 1 expression
- 1-evi
- mds 1-evi
- group
- mds 1-evi expression
- leukemia
- aml patients
- sample
- table
- analysis
- value
- abnormality
- karyotype
- survival
- myeloid leukemia
- mds 1 expression
- marrow
