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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >OVEREXPRESSION OF DR-NM23, A PROTEIN ENCODED BY A MEMBER OF THE NM23 GENE FAMILY, INHIBITS GRANULOCYTE DIFFERENTIATION AND INDUCES APOPTOSIS IN 32DC13 MYELOID CELLS
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OVEREXPRESSION OF DR-NM23, A PROTEIN ENCODED BY A MEMBER OF THE NM23 GENE FAMILY, INHIBITS GRANULOCYTE DIFFERENTIATION AND INDUCES APOPTOSIS IN 32DC13 MYELOID CELLS

机译：DR-NM23（NM23基因家族成员编码的蛋白）的过表达抑制32DC13骨髓细胞中粒细胞的分化并诱导其凋亡。

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Chronic myelogenous leukemia evolves in two clinically distinct stages: a chronic and a blast crisis phase. The molecular changes associated with chronic phase to blast crisis transition are largely unknown, We have identified a cDNA clone, DR-nm23, differentially expressed in a blast-crisis cDNA library, which has approximate to 70% sequence similarity to the putative metastatic suppressor genes, nm23-H1 and nm23-H2. The deduced amino acid sequence similarity to the proteins encoded by these two latter genes is approximate to 65% and includes domains and amino acid residues (the leucine zipper-like and the RGD domain, a serine and a histidine residue in the NH2- and in the COOH-terminal portion of the protein, respectively) postulated to be important for nm23 function. DR-nm23 mRNA is preferentially expressed at early stages of myeloid differentiation of highly purified CD34(+) cells, Its constitutive expression in the myeloid precursor 32Dc13 cell line, which is growth-factor dependent for both proliferation and differentiation, results in inhibition of granulocytic differentiation induced by granulocyte colony-stimulating factor and causes apoptotic cell death. These results are consistent with a role for DR-nm23 in normal hematopoiesis and raise the possibility that its overexpression contributes to differentiation arrest, a feature of blastic transformation in chronic myelogenous leukemia. [References: 32]
机译：慢性粒细胞性白血病在两个临床上不同的阶段发展：慢性阶段和爆炸危机阶段。与慢性阶段到胚芽危机过渡有关的分子变化在很大程度上是未知的，我们已经鉴定了在胚芽危机cDNA文库中差异表达的cDNA克隆DR-nm23，其与假定的转移抑制基因的序列相似性约为70％ ，nm23-H1和nm23-H2。推导的氨基酸序列与后两个基因编码的蛋白质的相似性约为65％，包括结构域和氨基酸残基（亮氨酸拉链状和RGD结构域，NH2和NH4中的丝氨酸和组氨酸残基）。分别假设蛋白质的COOH末端部分）对nm23功能很重要。 DR-nm23 mRNA在高度纯化的CD34（+）细胞的髓系分化的早期阶段优先表达，其在髓系前体32Dc13细胞系中的组成型表达（其依赖于生长因子的增殖和分化）导致对粒细胞的抑制粒细胞集落刺激因子诱导的分化并导致凋亡细胞死亡。这些结果与DR-nm23在正常造血中的作用一致，并增加了其过度表达有助于分化停滞的可能性，这是慢性粒细胞性白血病中转化的特征。 [参考：32]

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