Expression and methylation status of the FHIT gene in acute myeloid leukemia and myelodysplastic syndrome
Expression and methylation status of the FHIT gene in acute myeloid leukemia and myelodysplastic syndrome
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DOI：
10.1038/sj.leu.2403805
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发表时间：
2005-08-01
期刊：
影响因子：
11.4
通讯作者：
Naoe, T
中科院分区：
文献类型：
--
作者：
Iwai, M;Kiyoi, H;Naoe, T
为了阐明脆性组氨酸三联体（FHIT）在血液系统恶性肿瘤中的作用，我们检测了骨髓增生异常综合征（MDS）和急性髓性白血病（AML）细胞中FHIT基因的甲基化状态和表达水平，并与p15（INK4B）基因的甲基化进行比较。FHIT基因甲基化在94例AML和40例MDS中分别为13例（13.8%）和22例（55.0%），而在正常单核细胞中均未发现。甲基化的频率和密度在晚期MDS和复发AML病例中均增加。虽然FHIT和p15（INK4B）甲基化在MDS和AML中不相关，但AML复发时FHIT甲基化增加与p15（INK4B）甲基化相关。AML中的中位表达水平显著高于正常MNC，尽管甲基化的中位表达水平显著低于未甲基化的中位表达水平。此外，AML复发时的甲基化水平显著高于诊断时。提示FHIT基因甲基化在MDS和AML的发病过程中均存在积累，FHIT基因在AML和MDS中的抑癌作用可能不同。
To clarify the role of fragile histidine triad ( FHIT) in hematological malignancies, we examined the methylation status and the expression level of the FHIT gene in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) cells in comparison with the methylation of the p15(INK4B) gene. The FHIT methylation was found in 13 of 94 (13.8%) AML and 22 of 40 (55.0%) MDS cases, but not in normal mononuclear cells (MNCs). Both the frequency and density of methylation increased in the advanced-stages MDS and the relapsed AML cases. Although FHIT and p15(INK4B) methylations were not correlated in MDS and AML, increased FHIT methylation at the relapse in AML was associated with p15(INK4B) methylation. The median expression level in AML was significantly higher than in normal MNCs, although the median expression level in those with methylation was significantly lower than in those without methylation. Furthermore, the methylation level at relapse was significantly higher than at diagnosis in AML. These results suggested that FHIT methylation was accumulated through the disease progression of MDS and AML, and the role of the FHIT gene as a tumor suppressor seemed different in AML and MDS.