title: High EVI1 expression predicts poor survival in acute myeloid leukemia: a study of 319 de novo AML patients.
abstract: 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.
authors.affiliation: Institute of Hematology, Erasmus Medical Centre, Rotterdam, Netherlands.
authors.forename: Sahar
authors.initials: S
authors.lastname: Barjesteh van Waalwijk van Doorn-Khosrovani
authors.forename: Claudia
authors.initials: C
authors.lastname: Erpelinck
authors.forename: Wim L J
authors.initials: WL
authors.lastname: van Putten
authors.forename: Peter J M
authors.initials: PJ
authors.lastname: Valk
authors.forename: Sonja
authors.initials: S
authors.lastname: van der Poel-van de Luytgaarde
authors.forename: Ronald
authors.initials: R
authors.lastname: Hack
authors.forename: Rosalyn
authors.initials: R
authors.lastname: Slater
authors.forename: Elisabeth M E
authors.initials: EM
authors.lastname: Smit
authors.forename: H Berna
authors.initials: HB
authors.lastname: Beverloo
authors.forename: Gregor
authors.initials: G
authors.lastname: Verhoef
authors.forename: Leo F
authors.initials: LF
authors.lastname: Verdonck
authors.forename: Gert J
authors.initials: GJ
authors.lastname: Ossenkoppele
authors.forename: Pieter
authors.initials: P
authors.lastname: Sonneveld
authors.forename: Georgine E
authors.initials: GE
authors.lastname: de Greef
authors.forename: Bob
authors.initials: B
authors.lastname: Löwenberg
authors.forename: Ruud
authors.initials: R
authors.lastname: Delwel
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D001853:Bone Marrow; D016022:Case-Control Studies; D002869:Chromosome Aberrations; D002893:Chromosomes, Human, Pair 3; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D006801:Humans; D007951:Leukemia, Myeloid / Q000378:metabolism* / Q000401:mortality* / Q000628:therapy; D000074008:MDS1 and EVI1 Complex Locus Protein; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D015514:Oncogene Proteins, Fusion; D016133:Polymerase Chain Reaction; D011379:Prognosis; D000090063:Proto-Oncogene Mas; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000032:analysis; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D016019:Survival Analysis; D014157:Transcription Factors; D016896:Treatment Outcome
chemical_list: D004268:DNA-Binding Proteins; C000715470:MAS1 protein, human; D000074008:MDS1 and EVI1 Complex Locus Protein; C098704:MDS1-EVI1 fusion protein, human; C063575:MECOM protein, human; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors