title: Expression and prognostic significance of different mRNA 5'-end variants of the oncogene EVI1 in 266 patients with de novo AML: EVI1 and MDS1/EVI1 overexpression both predict short remission duration.
abstract: Rearrangements of chromosome band 3q26.2 lead to overexpression of the EVI1 gene and are associated with a poor prognosis in myeloid malignancies. EVI1 is also overexpressed in some cases without 3q26 rearrangements. To uncover its prognostic significance in this patient group, however, it may be necessary to distinguish among several known 5'-end variants of its mRNA. According to a recent report, overexpression of the transcript variant EVI1_1d was associated with shortened survival in acute myeloid leukemia (AML), but overexpression of MDS1/EVI1, whose protein product differs structurally and functionally from that of all other known EVI1 5'-end variants, was not. The aim of the present study was to determine, for the first time, the expression and prognostic significance of all known EVI1 5'-end variants in AML. Quantitative RT-PCR was used to measure the expression of EVI1_1a, EVI1_1b, EVI1_1d, EVI1_3L, and MDS1/EVI1 in 266 samples from patients with de novo AML. To correlate expression of the EVI1 5'-end variants with survival parameters, regression analyses were performed. 41/266 patients (15.4%) overexpressed at least one, but more often several or all, EVI1 transcript type(s). High expression of each of the EVI1 mRNA variants, including MDS1/EVI1, was significantly associated with shortened continuous complete remission in the total patient population as well as in the subgroups of patients with intermediate risk or normal cytogenetics. The present study therefore shows that high levels of each of the known EVI1 mRNA 5'-end variants represents an adverse prognostic factor in de novo AML without 3q26 rearrangements. This article contains Supplementary Material available at http://www.interscience.wiley.com/jpages/1045-2257/suppmat.
authors.affiliation: Department of Medical Genetics, Medical University of Vienna, Vienna, Austria.
authors.forename: Katja
authors.initials: K
authors.lastname: Haas
authors.forename: Michael
authors.initials: M
authors.lastname: Kundi
authors.forename: Wolfgang R
authors.initials: WR
authors.lastname: Sperr
authors.forename: Harald
authors.initials: H
authors.lastname: Esterbauer
authors.forename: Wolf-Dieter
authors.initials: WD
authors.lastname: Ludwig
authors.forename: Richard
authors.initials: R
authors.lastname: Ratei
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Koller
authors.forename: Helga
authors.initials: H
authors.lastname: Gruener
authors.forename: Cristina
authors.initials: C
authors.lastname: Sauerland
authors.forename: Christa
authors.initials: C
authors.lastname: Fonatsch
authors.forename: Peter
authors.initials: P
authors.lastname: Valent
authors.forename: Rotraud
authors.initials: R
authors.lastname: Wieser
mesh_terms: D020121:5' Untranslated Regions / Q000235:genetics* / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015973:Gene Expression Regulation, Leukemic / Q000502:physiology*; D015321:Gene Rearrangement; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D000074008:MDS1 and EVI1 Complex Locus Protein; D008297:Male; D008875:Middle Aged; D015514:Oncogene Proteins, Fusion / Q000235:genetics* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011519:Proto-Oncogenes / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D012074:Remission Induction; D012189:Retrospective Studies; D015996:Survival Rate; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D020121:5' Untranslated Regions; D004268:DNA-Binding Proteins; D000074008:MDS1 and EVI1 Complex Locus Protein; C098704:MDS1-EVI1 fusion protein, human; C063575:MECOM protein, human; D015514:Oncogene Proteins, Fusion; D012333:RNA, Messenger; D014157:Transcription Factors