Expression of EVI1 in myelodysplastic syndromes and other hematologic malignancies without 3q26 translocations

Abstract

The EVI1 gene encodes a zinc-finger, DNA-binding protein originally described as the transforming gene associated with a common ecotropic viral insertion site in myeloid leukemias. Previous studies demonstrated EVI1 expression in human leukemias in cases with 3q26 translocations, but not in normal blood or bone marrow. These studies also suggested an association between EVI1 expression and chromosome 7 deletion (del). Because of this association, we examined expression of EVI1 using RNA polymerase chain reaction (PCR) in patients with myelodysplastic syndromes (MDS) and acute leukemia with and without 3q26 translocations. EVI1 RNA was expressed in 29% of 34 (95% confidence interval, 20% to 50%) patients with the MDS subtypes refractory anemia (RA), refractory anemia with excess blasts (RAEB), or refractory anemia with excess blasts in transformation (RAEB-T). The vast majority of these cases occurred in patients with RAEB and RAEB-T. EVI1 expression was not detected in patients with chronic myelomonocytic leukemia (CMML), normal bone marrow or cord blood, or a variety of other hematologic malignancies. EVI1 RNA was detected in three of 18 patients with acute myelogenous leukemia (AML) and in two of four patients with acute promyelocytic leukemia (APL). Karyotypes showed that only one AML patient had karyotype 3q26 abnormalities, indicating that EVI1 expression is associated with cases that do not have structural abnormalities involving chromosome 3q26. These studies document for the first time the abnormal expression of EVI1 RNA by patients with MDS, and suggest an important role for EVI1 in the pathogenesis or progression of some myeloid malignancies.

Genetic Abnormalities as Targets for Molecular Therapies in Myelodysplastic Syndromes

“…Specific chromosomal abnormalities involving bands 3q21 and 3q26 have been observed in MDS. [58][59][60][61] The rearrangements encountered are the paracentric inversion inv(3)(q21;q26) and a reciprocal translocation t(3;3)(q21;q26). 62 A recurrent translocation or inversion between the regions of 3q21 and 3q26 gives rise to the so-called 3q21q26 syndrome, which is found in 0.5-2% of adult patients with MDS.…”

“…The 3q26.2 chromosome band contains the EVI1 proto-oncogene, which has been demonstrated to be involved in the pathogenesis of human AMLs and MDS. 58,59,61 Although these rearrangements are infrequent in MDS, they are of remarkable prognostic value. In normal tissues, EVI-1 is also found in a longer isoform, named MDS-EVI1, which encodes a protein with an additional proximal extension of 188 amino acids, which results from the splicing from exon 2 of the MDS1 gene to the second exon of EVI1.…”

Myelodysplastic Syndromes

“…Specific chromosomal abnormalities involving bands 3q21 and 3q26 have been observed in MDS. [28][29][30][31] The rearrangements encountered are the paracentric inversion inv(3)(q21q26) and a reciprocal translocation t(3;3)(q21;q26). 32 A recurrent translocation or inversion between the regions of 3q21 and 3q26 gives rise to the socalled 3q21q26 syndrome,' which is found in 0.5 to 2 percent of adult patients with MDS.…”

“…The 3q26.2 chromosome band contains the EVI-1 proto-oncogene, which has been demonstrated to be involved in the pathogenesis of human acute myeloid leukemia (AML) and myelodysplastic syndromes. 28,29,31 Although these rearrangements are infrequent in MDS, they are of remarkable prognostic value.…”

Mapping of leukaemia‐associated breakpoints in chromosome band 3q21 using a newly established PAC contig

“…However, its possible physiological functions in haematopoiesis as well as its transcriptional targets remain to be elucidated. Also, its aberrant expression is not strictly correlated with the presence of chromosome aberrations involving band 3q26 (Russell et al, 1994;Fontenay Roupie et al, 1997;Xi et al, 1997).…”