原发性骨髓增生异常综合征患者NPM1基因突变的研究

目的 探讨原发性骨髓增生异常综合征(MDS)患者NPM1基因突变情况及其与MDS患者临床特征的关系.方法 对232例原发性MDS患者采用基因组DNA聚合酶链反应(PCR)扩增NPM1基因第12外显子,直接测序检测突变状态,克隆后测序鉴定突变类型.比较NPM1突变患者与野生型患者的临床及实验室特征.结果 232例患者中NPM1突变9例(3.9%),均为A型突变.NPM1突变患者中性粒细胞绝对值(ANC)较低[突变型和野生型患者分别为0.60(0.12～2.91)×109/L和1.02(0～10.23)×109/L,P=0.046],骨髓原始细胞比例较高[突变型和野生型患者分别为0.050(0～0.090)和0.025(0～0.190),P=0.035],干/祖细胞培养后红系爆式集落(BFU-E)数量减低[突变型和野生型患者105个骨髓单个核细胞中集落数分别为0(0～0)和6(0～40),P=0.038],血清维生素(Vit)B12水平较高[突变型和野生型患者分别为936.40(373.80～2400.00)pmol/L和557.85(17.00～3032.10)pmol/L,P=0.045].NPM1突变患者以正常核型为主.结论 NPM1基因突变的MDS患者具有一些独特的临床和实验室特征,此为进一步研究NPM1基因突变与原发性MDS发生及转变为白血病的关系提供了重要线索.

Study on NPM1 gene mutations in patients with primary myelodysplastic syndromes

Objective To investigate NPM1 gene mutations in patients with primary myelodysplastic syndromes (MDS) and the clinical characteristics of patients with NPM1 mutants. Methods Genomic DNA Corresponding to exon 12 of NPM1 gene was amplified by polymerase chain reaction(PCR) in 232 patients with primary MDS. Identification of mutants was by direct sequencing and classification of mutation types by sequencing followed by plasmid cloning. Results NPM1 mutants were found in 9 patients(3.9% ) . All the mutants were type A. As compared with those with NPM1 wild type, patients with the mutant were of lower ANC [0.60 (0. 12 - 2.91 ) × 109/L vs 1.02 (0 - 10. 23 ) × 109/L, P = 0.046], higher blast percent in bone marrow [0.050(0 -0. 090) vs 0. 025(0 -0. 190) ,P =0. 035], decreased BFU-E[0(0 -0)/105 BMMNC vs 6(0 - 40 )/105 BMMNC, P = 0. 038]and increased serum vitamin B17 [936.40 ( 373.80 -2400.00) pmol/L vs 557.85 ( 17.00 - 3032.10) pmol/L, P = 0.045]The chromosomal karyotypes of patients with NPM1 mutant were predominantly normal. Conclusion MDS patients with NPM1 gene mutations have some unique clinical and laboratory features. The results give new hint for the pathogenesis of MDS development and progression.