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
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
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DOI：
10.1182/blood.v96.9.3209.h8003209_3209_3214
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发表时间：
2000-11-01
期刊：
影响因子：
20.3
通讯作者：
Morishita, K
中科院分区：
文献类型：
--
作者：
Mochizuki, N;Shimizu, S;Morishita, K
t（1;3）（p36;q21）相互易位发生在骨髓增生异常综合征（MDS）和急性髓性白血病（AML）的一个亚群中，其通常以三系发育异常，特别是巨核细胞生成异常和预后不良为特征。以前，3q 21处的断裂点簇区（BCR）被鉴定为位于3q 21 q26综合征BCR着丝粒的60 kb区域内，而1p36.3处的BCR位于90 kb区域内。在这项研究中，基因附近的断点在1p36.3搜索，并分离出一个新的基因，编码锌指蛋白与PR结构域，这是高度同源的MDS 1/EVI 1基因。MEL 1（MDS 1/EVI 1-like gene 1）与MDS 1/EVI 1的核苷酸同源性为64%，氨基酸同源性为63%，具有相同的结构域。MEL 1基因在具有t（1;3）的白血病细胞中表达，但在其它细胞系或骨髓、脾和胎肝中不表达，这表明MEL 1特异性地在t（1;3）中（p36; q21）阳性MDS/AML，根据各易位中EVI 1和MEL 1基因的位置关系，这表明这两个基因都是通过3q 21区域与Ribophorin 1基因的易位而被转录激活的。由于t（1;3）（p36;q21）阳性MDS/AML和3q 21 q26综合征中EMI家族基因的转录激活，表明它们具有共同的细胞白血病转化的分子机制。(C)2000年，美国血液学会。
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 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 that they share a common molecular mechanism for the leukemogenic transformation of the cells. (C) 2000 by The American Society of Hematology.