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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。
With the development of a new generation of gene sequencing technology, more and more genes related to tumorigenesis have been found, such as the recently discovered DNMT3a gene. This gene provides a new molecular marker for the prognosis of acute myeloid leukemia. This study was to investigate the mutation of DNMT3a gene in the bone marrow of children with acute myeloid leukemia. Fifty-seven children with acute myeloid leukemia were selected from children’s blood disease diagnosis and treatment center of Hematology Hospital of Chinese Academy of Medical Sciences. All 23 exons of DNMT3a gene were amplified by PCR directly from their bone marrow cells. Type DNMT3a gene alignment, detection of DNMT3a gene mutations. The results showed that no mutations in the R882 locus of DNMT3a mutation were found in 57 children, and no mutation was found in any of the other loci. In these children, there were 10 cases of AML1 / ETO mutation, 3 cases of CBFB / MYH11 mutation, 13 cases of PML / RARa mutation, 5 cases of FLT3 / ITD mutation and 1 case of FLT3 / TKD mutation, which contained both PML / RARa and FLT3 / TKD mutation in 2 cases. Conclusion: Although DNMT3a gene has a high mutation rate in adult patients with acute myeloid leukemia and is an independent factor of poor prognosis, its mutation rate is very low in children with no mutation. This suggests that there may be different mechanisms for the occurrence of acute myeloid leukemia in children and adults.