A novel gene, MEL1, mapped to 1p36.3 is highly homologous to the MDS1/EVI1gene and is transcriptionally activated in t(1;3)(p36;q21)-positive leukemia cells

The reciprocal translocation t(1;3)(p36;q21) occurs in a subset of myelodys plastic syndrome (MDS) and acute myeloid leukemia (AML), which is frequentl y characterized by trilineage dysplasia, in particular dysmegakaryocytopoie sis, and poor prognosis. Previously, the breakpoint cluster region (BCR) at 3q21 was identified within a 60-kilobase (kb) region centromeric to the BC R of 3q21q26 syndrome and that at 1p36.3 within a 90-kb region. In this stu dy, genes were searched near the breakpoints at 1p36.3, and a novel gene wa s isolated that encoded a zinc finger protein with a PR domain, which is hi ghly homologous to the MDS1/EVI1 gene. The novel gene, designated as MEL1 ( MDS1/EVI1-like gene 1), with 1257 amino acid residues is 64% similar in nuc leotide and 63% similar in amino acid sequences to MDS1/EVI1 with the same domain structure. The MEL1 gene is expressed in leukemia cells with t(1;3) but not in other cell lines or bone marrow, spleen, and fetal liver, sugges ting that MEL1 is specifically in the t(1;3)(p36;q21)positive MDS/AML, On t he basis of the positional relationship between the EVI1 and MEL1 genes in each translocation, it was suggested that both genes are transcriptionally activated by the translocation of the 3q21 region with the Ribophorin1 gene . Because of the transcriptional activation of the EMI family genes in both t(1;3)(p36;q21)-positive MDS/AML and 3q21q26 syndrome, it is suggested tha t they share a common molecular mechanism for the leukemogenic transformati on of the cells. (C) 2000 by The American Society of Hematology.