儿童急性髓系白血病DNMT3a基因突变的分析

随着新一代基因测序技术的发展,越来越多与肿瘤发生发展有关的基因被发现,比如最近发现的DNMT3a基因。此基因为急性髓系白血病预后判断提供了新的分子生物学标记。本研究探讨儿童急性髓系白血病患儿骨髓中DNMT3a基因的突变情况。选取就诊于中国医学科学院血液病医院儿童血液病诊治中心的57例儿童急性髓系白血病患儿,通过PCR直接扩增其骨髓细胞中DNMT3a基因全部23个外显子,并通过直接测序方法与野生型DNMT3a基因比对,检测DNMT3a基因的突变情况。结果表明,在57例患儿中未发现DNMT3a突变热点R882位点的突变,进一步分析其它位点也未发现任何突变。而在这些患儿中AML1/ETO突变10例,CBFB/MYH11突变3例,PML/RARa突变13例,FLT3/ITD突变5例,FLT3/TKD突变1例,既含有PML/RARa又含有FLT3/TKD突变2例。结论:DNMT3a基因虽然在成人急性髓系白血病患者中有着较高的突变率,且是预后不良的一个独立因素,但其突变率在儿童患者中很低,甚至没有突变。这提示儿童和成人急性髓系白血病的发生可能存在不同机制。

Analysis of DNMT3a Mutation in Childhood Acute Myeloid Leukemia

Within the past few years, the invention of next-generation sequencing has revealed several new genes associated with tumor formation and development, for example DNMT3α. This gene is an independent prognostic factor for acute myeloid leukemia （AML）. The objective of this study was to analyze the DNMT3α mutation in childhood AML in a single center. PCR amplification of the entire coding region of DNMT3α was performed using 23 overlapping primer pairs in 57 patients who were diagnosed in Blood Disease Hospital of Chinese Academy of Medical Sciences, then the directly sequencing was underwent. The results showed that no DNMT3α mutation was found in these patients including the hotspot R882. But AML1/ETO mutation was found in 10 patients, CBFB/MYH11 mutation in 3 patients, PML/RARa mutation in 13 patients, FLT3/ITD mutation in 5 patients, FLT3/TKD mutation in 1 patient, PML/RARa and FLT3/TKD mutation coexisted in 2 patients. It is concluded that DNMT3α mutations are rare in childhood AML, and different mechanisms of myeloid leukemogenesis between childhood and adults maybe involved.