急性早幼粒细胞白血病中常见白血病基因突变的检测及其临床意义

本研究旨在探讨多种常见白血病基因突变是否协同参与急性早幼粒细胞白血病(APL)的发病机制,探讨这些突变与APL患者的临床表现、细胞遗传学及分子危险度分层的关系。收集了2005年2月至2010年1月收治的84例初治APL患者标本,采用基因组DNA-PCR方法分析骨髓单个核细胞中各个基因的突变情况及突变阳性患者的临床特征。结果表明,84例APL患者中合并突变的患者51例(60.7%),其中FLT3-ITD突变发生率最高,达到27.4%(23/84);其次,WT1突变12例,FLT3-TKD突变9例,TET2突变7例,N-RAS突变5例,ASXL1突变4例,EZH2突变2例,MLL-PTD、IDH1及CBL各突变1例;而JAK1、DNMT3、c-Kit、NPM1、IDH2、RUNX1、JAK2(V617F)等常见白血病相关基因未发现突变。结合临床资料,FLT3-ITD突变阳性患者的白细胞计数较高,N-RAS突变阳性患者的血小板计数较低,与野生型患者相比差异均有统计学意义(P<0.05);具有FLT3-ITD突变或N-RAS突变的患者总体生存期较无相关突变组患者明显缩短,差异有统计学意义(P<0.05)。单纯t(15;17)易位(69/84)患者与附加其他染色体异常(13/84)患者的总体生存时间无明显差别。结论:FLT3-ITD突变是APL患者常见的分子突变类型,其与N-RAS突变均为APL患者的不良预后因素;APL中合并其他染色体异常不影响患者的总体生存期。

Clinical Significance of Common Leukemia Gene Mutations in Patients with Acute Promyelocytic Leukemia

This study was aimed to explore whether multiple common gene mutations of leukemia synergestically involved in acute promyelocytic leukemia （APL） pathogenesis, and to investigate their relevance to clinical features, cytogenetics and molecular risk stratification. 84 specimens of admitted de novo APL patients from February 2005 to October 2010 were collected, the gene mutations of bone marrow mononuclear cells and clinical features of mutation-positive patients were analyzed by genomic DNA-PCR. The results indicated that the prevalence of mutations was 60. 7% （51/84）, in which the mutations with the highest incidence were found as FLT3-ITD, reaching 27.4% （23/84）. Next, there were 12 cases WTI mutation, 9 for FLT3-TKD, 7 for TET2, 5 for N-RAS, 4 for ASXL1,2 for EZH2 mutation and 1 positive case in MLL-PTD, IDH1 and CBL mutation respectively. No mutation was found in other JAK1, DNMT3, c-Kit, NPM1, IDH2, RUNX1 and JAK2 （V617F） common leukemia-related genes. Combined anatysis with clinical data demonstrated that the patients with FLT3-1TD mutation displayed higher white blood cell counts, while the patients with N-RAS mutation showed lower platelet counts. Overall survival of these patients was obviously shorten as compared with patients with wild-type. This difference between mutant and wild-type of all above mentioned cases was statistically significant （ P 〈 0.05 ）. The difference between APL with simple t （ 15 ; 17 ） and additional abnormal karyotype was not statistically significant. It is concluded that the FLT3-ITD mutation is recurrent genetic change in APL, and together with N-RAS mutation indicates poor prognosis. Additional abnormal karyotype does not associate with prognosis of APL.