Nm23 gene expression and cellular growth and differentiation

分化抑制因子/nm 23蛋白可抑制小鼠和人髓系白血病细胞的分化。分化阻滞可能与白血病的侵袭行为有关。为了检测nm 23在人髓性白血病细胞生长和分化中的作用，我们研究了正常血细胞、正常骨髓细胞、白血病细胞系、逆转录聚合酶链反应检测急性髓系白血病（AML）患者白血病细胞和正常对照细胞中nm 23-H1和nm 23-H2的表达水平。nm 23-H1 mRNA表达水平与AML患者的预后有关，nm 23-H1 mRNA表达水平与AML患者的临床参数相关性分析表明，nm 23-H1 mRNA表达水平升高与初治化疗耐药及总生存期降低有关。多因素分析提示，nm 23-H1 mRNA水平升高与AML患者的预后有关，尤其是AML-M5患者。我们通过Western blot、免疫组化染色和流式细胞术分析证实了nm 23蛋白在白血病细胞中的过度表达。所有白血病细胞系均表达nm 23-H1蛋白，而正常血细胞和骨髓细胞均不表达nm 23-H1蛋白。这些结果表明nm 23蛋白的细胞表面表达对于白血病细胞是特异性的。

The differentiation inhibitory factor /nm23 protein can inhibit the differentiation of murine and human myeloid leukemia cells. Block of differentiation may be associated with the aggressive behavior of leukemia. To examine the role of nm23 in growth and differentiation of human myeloid leukemia cells, we investigated the relative levels of nm23-H1, nm23-H2 and c-myc transcripts in normal blood cells, normal bone marrow cells, leukemic cell lines, and leukemic cells from patients with acute myeloid leukemia (AML) by reverse transcriptase polymerase chain reaction.Expression levels of nm23-H1 and nm23-H2 in leukemic cell lines and the AML samples were significantly higher than that in normal blood cells and a higher level of nm23-H1 expression was correlated with a poor prognosis in AML.An analysis of the correlation between nm23 expression and the clinical parameters demonstrated that increased nm23-H1 mRNA levels were associated with resistance to initial chemotherapy and with reduced overall survival. Multivariate analysis of putative prognostic factors revealed that elevated nm23-H1 mRNA levels significantly contributed to the prognosis of patients with AML,especially in AML-M5.We confirmed the overexpresion of nm23 proteins in leukemic cells by Western blot, immunohistochemical staining, and flow cytometrical analysis. All leukemic cell lines examined expressed nm23-H1 protein on the cell surface, but the normal blood and bone marrow cells did not. These results show that the cell surface expression of nm23 protein is specific for leukemic cells.