Serum nm23-H1 protein as a prognostic factor in hematological malignancies
Serum nm23-H1 protein as a prognostic factor in hematological malignancies
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DOI：
10.1080/10428190290017006
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发表时间：
2002-04-01
影响因子：
2.6
通讯作者：
Okabe-Kado, J
中科院分区：
文献类型：
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作者：
Okabe-Kado, J
非分化小鼠髓性白血病细胞系产生分化抑制因子。这些因素之一被纯化为nm 23的同源物。nm 23基因作为转移抑制基因被分离，其在高水平转移性癌细胞中表现出低表达。nm 23基因在急性髓细胞白血病（AML）细胞中过表达，nm 23-H1高表达与AML预后不良相关。多因素分析提示nm 23-H1 mRNA水平升高与AML患者的预后密切相关。nm 23-HI在多种血液肿瘤中也有过表达。为了利用nm 23过表达来判断淋巴瘤的预后，我们建立了酶联免疫吸附试验（ELISA）技术来测定血清nm 23-H1蛋白水平。该方法比用逆转录-聚合酶链反应（RT-PCR）测定nm 23 mRNA的方法简单得多。使用该系统，我们测量了许多血液恶性肿瘤中的nm 23-H1蛋白水平。血清nm 23-H1水平显着高于所有的血液肿瘤患者测试（AML，慢性粒细胞白血病，急性淋巴细胞白血病，（ALL）骨髓增生异常综合征（MDS）和恶性淋巴瘤）比正常对照组。血清nm 23-H1蛋白浓度升高预示AML和非霍奇金淋巴瘤预后不良。尤其是在弥漫性大B细胞淋巴瘤（DLBCL）中，血清nm 23-H1蛋白水平是制定DLBCL治疗策略的重要预后因素。血清nm 23-H1蛋白水平可能依赖于nm 23-H1过表达的恶性肿瘤细胞的总质量。
A nondifferentiating mouse myeloid leukemia cell line produces differentiation-inhibiting factors. One of these factors was purified as a homologue of nm23. The nm23 gene was isolated as a metastasis-suppressor gene that exhibits low expression in high-level metastatic cancer cells. The nm23 gene was overexpressed in acute myelogenous leukemia (AML) cells and a higher level of nm23-H1 expression was correlated with a poor prognosis in AML. Multivariate analysis of putative prognostic factors revealed that elevated nm23-H1 mRNA levels significantly contributed to the prognosis of patients with AML. The overexpression of nm23-HI was also observed in various hematological neoplasms. To use nm23 overexpression to determine the prognosis for lymphoma, we established an enzyme-linked immunosorbent assay (ELISA) technique to determine the serum level of nm23-H1 protein. This assay is far simpler than that used to determine nm23 mRNA by reverse transcriptase-polymerase chain reaction (RT-PCR). Using this system, we measured nm23-H1 protein levels in many hematological malignancies. Serum nm23-H1 levels were significantly higher in patients with all of the hematological neoplasms tested (AML, chronic myelogenous leukemia, acute lymphoblastic leukemia, (ALL) myelodysplastic syndrome (MDS) and malignant lymphomas) than in normal controls. An elevated serum nm23-H1 protein concentration predicted a poor outcome for AML and non-Hodgkin's lymphoma. Especially in diffuse large B-cell lymphoma (DLBCL), serum nm23-H1 protein levels were an important prognostic factor in planning an appropriate treatment strategy for DLBCL. The serum nm23-H1protein levels probably depend on the total mass of malignant cells overexpressing nm23-H1.