急性单核细胞白血病新抗原MLAA-34基因突变的检测及其与疗效相关性的研究

Detection of Novel Antigen MLAA-34 Gene Mutation in Acute Monocytic Leukemia and Its Correlation with Efficacy

目的:研究MLAA-34全外显子突变与白血病疗效的相关性。方法:对AML-M5组(40例)及健康对照组(5例),应用RT-PCR方法检测MLAA-34基因的表达水平,研究其对化疗疗效的影响。对该基因全部12个外显子进行测序,研究MLAA-34突变对M5患者OS和PFS的影响;分析白血病重要的5个预后基因突变与MLAA-34基因突变的相关性。结果:M5组MLAA-34基因表达显著高于正常对照组,高表达的患者化疗疗效差。E2外显子第59号碱基存在多态性,C59T位点突变的患者具有更高的MLAA-34基因表达。MLAA-34基因C59T位点突变与重要的分子标志基因FLT-3和DNMT3A的突变显著相关。结论:MLAA-34基因C59T位点突变为白血病复发的高危因素,并可成为一个白血病治疗的候选靶点。

Objective： To investigate the correlation of all exone mutation in MLAA-34 gene with chemotherapeutic efficacy for leukemia. Methods： The expression level of MLAA-34 gene in 40 patients with AML-M5 and 5 healthy volunteers as control was detected by RT-PCR and its effect on chemotherapeutic efficacy were analyzed by RT-PCR; the effect of MLAA-34 gene mutation on overall survival（ OS） and progression-free survival（ PFS） of AML-M5 patients was analyzed by sequencing of all 12 exoues in MLAA-34 gene,the correlation between the mutation of prognostic genes important to leukemia and the mutation of MLAA-34 gene was explored. Results： The expression level of MLAA-34 gene was significantly up-regulated as compared with that of healthy volunteers,moreover this up-regulation was related with a C59 T SNP site located in second exon of MLAA-34 gene,meanswhile this SNP site is affinitive to the well-known mdecular markers of AML,inclinding Fms-like tyrosine kinase（ FLT-3） and DNA methyltransferase-3 A（ DNAMT3 A）.The AML-M5 patients with high expression of MLAA-34 gene poorly responded to chemotherapy,the AML-M5 patients with MLAA-34 C59 T mulation had even more high expression of MLAA-34 gene and significantly short OS and PFS in comparison with those of patients without C59 T mutation. Conclusion： The C59 T mutation in MLAA-34 gene is a high risk factor for recurrence of AML,and may be a cadidate target for treatment of AML.