非髓性白血病的其他恶性血液病中DNMT3A基因突变的检测及临床意义

目的:了解DNMT3A基因突变在非髓性白血病的其他恶性血液肿瘤患者中的发生率、分布情况及临床意义.方法:选取196例非髓性白血病的其他血液肿瘤患者为研究对象,提取患者外周血基因组DNA,针对DNMT3A基因突变热点R882位点设计引物,采用聚合酶链式反应(PCR)法扩增DNMT3A基因23号外显子整个编码区基因片段,再将扩增产物纯化后测序,分析DNMT3A基因突变在本组恶性血液病患者中的发生率、分布情况及临床意义.结果:在57例非霍奇金淋巴瘤及34例骨髓增生异常综合征患者中各检出1例伴DNMT3A基因突变,在25例急性淋巴细胞白血病、45例多发性骨髓瘤和35例骨髓增殖性肿瘤患者中均未检测到DNMT'3A基因突变.结论:非髓性白血病的其他血液肿瘤患者中DNMT3A基因突变少见,伴DNMT3A基因突变的1例T淋巴母细胞白血病/淋巴瘤患者预后不良,联合去甲基化药物的化疗方案使伴该基因突变的1例骨髓增生异常综合征患者一度获得血液学完全缓解,但短期内转为急性白血病并发严重感染死亡.

Detection of DNMT3A gene mutation in hematologic malignancies except for myeloid leukemia and its clinical significance

Objective:To evaluate the rate of DNMT3A gene mutation in hematologic malignancies except for myeloid leukemia and evaluate its clinical value.Methods:Genomic DNA samples were extracted from 196 patients with hematologic malignancy.Polymerase Chain Reaction(RCR) was used to amplify the 23rd exon covering R882 codon,the mutational hotspot of DNMT3A gene.Then,sanger sequencing was performed to detect gene mutations of the purified DNA fragments.Results:One case with DNMT3A gene mutation was identified in 57 patients with non-Hodgkin lymphoma and in 34 patients with myelodysplastic syndrome (MDS),respectively.However,DNMT3A gene mutation was not detected in 25 patients with acute lymphoblastic leukemia,45 patients with multiple myeloma and 35 patients with myeloproliferative neoplasm.Conclusion:DNMT3A gene mutation is a rare event in hematologic malignancies except for myeloid leukemia.In our study,DNMT3A gene mutation was identified only in two patients,one case with T lymphoblastic leukemia/ lymphoma had a poor prognosis,the other diagnosed as MDS achieved completely hematologic remission after treatment with decitabine and chemotherapy,but soon progressed to acute leukemia.