A novel gene, MEL1, mapped to 1p36.3 is highly homologous to the MDS1/EVI1 gene and is transcriptionally activated in t(1;3)(p36;q21)-positive leukemia cells.
نویسندگان
چکیده
The reciprocal translocation t(1;3)(p36;q21) occurs in a subset of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), which is frequently characterized by trilineage dysplasia, in particular dysmegakaryocytopoiesis, and poor prognosis. Previously, the breakpoint cluster region (BCR) at 3q21 was identified within a 60-kilobase (kb) region centromeric to the BCR of 3q21q26 syndrome and that at 1p36.3 within a 90-kb region. In this study, genes were searched near the breakpoints at 1p36.3, and a novel gene was isolated that encoded a zinc finger protein with a PR domain, which is highly 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 nucleotide 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, suggesting that MEL1 is specifically in the t(1;3)(p36;q21)-positive MDS/AML. On the 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 Ribophorin I gene. Because of the transcriptional activation of the EVI1 family genes in both t(1;3)(p36;q21)-positive MDS/AML and 3q21q26 syndrome, it is suggested that they share a common molecular mechanism for the leukemogenic transformation of the cells.
منابع مشابه
A novel EVI1 gene family, MEL1, lacking a PR domain (MEL1S) is expressed mainly in t(1;3)(p36;q21)-positive AML and blocks G-CSF-induced myeloid differentiation.
We have identified a novel gene MEL1 (MDS1/EVI1-like gene 1) encoding a zinc finger protein near the breakpoint of t(1; 3)(p36;q21)-positive human acute myeloid leukemia (AML) cells. Here, we studied the structure, expression pattern, and function of MEL1 in leukemia cells. In this study, we have identified 3 transcription start sites, 1 in exon 1 and 2 in exon 2, and 2 kinds of translation pro...
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ورودعنوان ژورنال:
- Blood
دوره 96 9 شماره
صفحات -
تاریخ انتشار 2000