Combined analysis of differentiation inhibitory factor nm23-H1 and nm23-H2 as prognostic factors in acute myeloid leukaemia.
Combined analysis of differentiation inhibitory factor nm23-H1 and nm23-H2 as prognostic factors in acute myeloid leukaemia.
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DOI：
10.1038/bjc.1998.382
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发表时间：
1998-06
影响因子：
8.8
通讯作者：
Honma, Y
中科院分区：
文献类型：
--
作者：
Wakimoto, N;Yokoyama, A;Okabe-Kado, J;Nagata, N;Motoyoshi, K;Honma, Y
分化抑制因子（nm23蛋白）对多种白血病细胞系的分化诱导有抑制作用。我们之前报道过nm23基因（H1和H2）在急性髓性白血病（AML）中过表达，nm23-H1的表达预测AML的预后，尤其是AML- m5。为了阐明法-美-英（FAB）分类与nm23表达水平之间的相关性，并阐明nm23-H2和nm23- h1在患者生存中的作用，我们使用逆转录聚合酶链反应研究了76例AML样本中nm23- h1和-H2 mRNA的相对水平。我们证实nm23-H1和-H2基因在三家不同医院的AML样本中的表达均显著高于正常血细胞（P < 0.0005）。nm23-H1在FAB AML- m1、-M2、-M3、-M4和-M5亚型中均过表达，并在FAB AML-M2和-M5病例中显示nm23-H1表达对AML预后的预测作用。虽然nm23-H2在FAB各亚型中也有过表达，但在AML-M1和-M3细胞中nm23-H2的表达不明显高于正常细胞。AML亚型中，AML- m3两种nm23基因的表达水平最低。为了解nm23- h1和-H2表达水平的关系，绘制所有AML病例的nm23表达水平，并将其分为4组（A组，nm23- h1和-H2均高；B组，均低；C组，仅nm23- h1高；D组，仅nm23-H2高）。nm23-H1与-H2的表达水平有统计学意义（r= 0.726）。AML- m3多数属于B组，其他类型AML不属于B组。组间生存率分析显示，B组患者的生存时间明显长于a组，同一组AML- m3患者的生存时间也明显长于非m3患者。这些数据提示，nm23-H1和-H2的低表达水平与AML患者的良好预后相关。
Differentiation inhibitory factor (nm23 protein) inhibited the induction of the differentiation of various leukaemic cell lines. We previously reported that nm23 genes (H1 and H2) were overexpressed in acute myelogenous leukaemia (AML) and nm23-H1 expression predicted the prognosis of AML, especially AML-M5. To clarify the correlation between French-American-British (FAB) classification and nm23 expression level and to clarify the involvement of nm23-H2 and nm23-H1 in patient survival, we investigated the relative levels of nm23-H1 and -H2 mRNA in 76 AML samples using the reverse transcriptase-polymerase chain reaction. We confirmed that the expression of both nm23-H1 and -H2 genes in AML samples from three different hospitals was significantly higher than that in normal blood cells (P < 0.0005). Overexpression of nm23-H1 was observed in each FAB AML-M1, -M2, -M3, -M4 or -M5 subtype, and the predictive effect of nm23-H1 expression on AML prognosis was shown in FAB AML-M2 and -M5 cases. Although overexpression of nm23-H2 was also found in each FAB subtype, the expression of nm23-H2 in AML-M1 and -M3 cells was not significantly higher than that in normal cells. Among AML subtypes, AML-M3 showed the lowest expression levels of both nm23 genes. To understand the relationship between nm23-H1 and -H2 expression levels, nm23 expression levels for all the AML cases were plotted and divided into four groups (group A, nm23-H1 and -H2 both high; B, both low; C, only nm23-H1 high; D, only nm23-H2 high). A statistically significant correlation between the levels of expression of nm23-H1 and -H2 was observed (r= 0.726). Most AML-M3 cases belonged to group B, but not other types of AML. Analysis of survival probability between the groups showed that group B survived for significantly longer compared with group A. Furthermore, AML-M3 cases survived for significantly longer compared with non-M3 cases in the same group B. These data suggest that low expression levels of both nm23-H1 and -H2 are associated with good prognosis in AML patients.