Expression and prognostic significance of different mRNA 5 ' - End variants of the oncogene EVII in 266 patients with de novo AML: EVII and MDSI/EVII overexpression both predict short remission duration

Rearrangements of chromosome band 3q26.2 lead to overexpression of the EVII gene and are associated with a poor prognosis in myeloid malignancies. EVII 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 EVI_Id was associated with shortened survival in acute myeloid leukemia (AML), but overexpression of MDSI/EVII, whose protein product differs structurally and functionally from that of all other known EVII 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 EVII 5'-end variants in AML. Quantitative RT-PCR was used to measure the expression of EVI_Ia, EVII_Ib, EVI_Id, EVII_3L, and MDSI/EVII in 266 samples from patients with de novo AML. To correlate expression of the EVII 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, EVII transcript type(s). High expression of each of the EVII mRNA variants, including MDSI/EVII, 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 EVII mRNA 5'-end variants represents an adverse prognostic factor in de novo AML without 3q26 rearrangements.