正常核型急性髓系白血病NPM1、FLT3-ITD突变与外周血白细胞数及骨髓原始细胞百分比相关性研究  

Correlation of NPM1,FLT3-ITDmutations with Leukocyte Count and Myeloblasts Pencentage in AML Patients with Normal Karyotype

作　　者：苏龙[1] 李薇[1] 崔久巍[1] 谭业辉[1] 杨岩[1] 刘晓亮[1] 喻萍[1] 胡瑞萍[1] 王丽莉[1] 高素君[1] 

机构地区：[1]吉林大学白求恩第一医院肿瘤中心,吉林长春130021

出　　处：《中国实验血液学杂志》2013年第3期571-575,共5页Journal of Experimental Hematology

基　　金：吉林省卫生厅科研项目(编号2009Z067)

摘　　要：本研究旨在分析NPM1和FLT3-ITD突变与急性髓系白血病患者外周血白细胞数及骨髓原始细胞百分比的相关性。回顾分析我中心2009年1月至2011年12月份初治正常核型急性髓系白血病患者51例,其中男性22例,女性29例,中位年龄47岁(14-83岁)。采用聚合酶链式反应检测NPM1及FLT3-ITD突变状态。结果表明,与无NPM1突变患者相比,突变者初诊时外周血白细胞数较多(30.7×109/L vs 8.6×109/L,P=0.002);FLT3-ITD突变患者较无突变患者具有更多的外周血白细胞数(42.38×109/L vs 11.45×109/L,P=0.033)及更高的骨髓原始细胞百分比(74.0%vs 60.25%,P=0.036)。外周血白细胞数及骨髓原始细胞百分比在NPM1、FLT3-ITD无突变组、单独NPM1突变组、单独FLT3-ITD突变组到NPM1、FLT3-ITD双突变组逐步升高(均P<0.05)。白细胞数大于12.55×109/L的患者NPM1突变率明显升高(P=0.002),大于37.85×109/L者FLT3-ITD突变率明显升高(P=0.033);原始细胞比例大于72.25%的FLT3-ITD突变率明显升高(P=0.008)。NPM1突变患者首疗程完全缓解率(CR)明显高于无突变者(78.13%vs 40.0%,χ2=4.651,P=0.031)。结论:NPM1及FLT3-ITD突变患者白细胞计数及原始细胞比例大,提示NPM1与FLT3-ITD突变均可能促进白血病细胞增殖,且二者可能具有协同效应。This study was aimed to investigate the correlation of NPM1 and FLT3-1TD mutations with leukocyte count in peripheral blood and bone marrow blasts in patients with acute myeloid leukemia （AML）. Fifty-one acute mye loid leukemia patients with normal karyotype from January 2009 to December 2011 were enrolled in this study. The clini cal data of 51 cases were analyzed retrospectively. Out of 52 cases 22 were male, and 29 were female. The median age was 47 years old （ranged from 14 to 83 years old）. The de novo patients were examined by bone marrow cytomorpholo gy and blood routine analysis. Polymerase chain reaction was used to analyze the NPM1 and FLT3-1TD mutations. The results showed that the patients with NPM1 mutations had higher leukocyte count compared with those without mutations （30.7 x 109/L vs 8.6 x 109/L, P =0.002）. FLT3-1TD mutation was related to higher leukocyte count （42. 38 x 109/L vs 11.45 x 109/L without mutation, P =0. 033） and blasts （74.0% vs 60.25% without mutation, P =0. 036）. The leukocyte count and percentage of bone marrow blasts were lowest in the patients with neither mutations, and gradually increasing in the NPM1 - mutation, FLT3-1TD- mutation, and NPM1 ＋ mutation, FLT3-1TDI＋ mutation, and NPM1 / FLT3-1TD mutation groups （P〈0.05）. The patients tended to have NPM1 （P=0.002） and FLT3-1TD （P =0.033） mutations when their leukocyte counts were more than 12.55 x 109/L and 37.85 x 109/L, respectively. Those with bone marrow blast more than 72.25 % showed higher rate of FLT3-1TD mutation （ P = 0.008 ）. Patients with NPM1 mutations had higher complete remission rate than those without NPM1 mutation （78.13% vs 40.0%, X2 = 4. 651, P = 0. 031 ） after remission induction therapy. It is concluded that both NPMI and FLT3-ITD mutations are linked to higher leukocyte count and blast percentage, suggesting that both mutations may be associated with increased proliferation of leukemia cells, and may have a synergistic function in stimulating proliferation.

关 键 词：急性髓系白血病 正常核型 白细胞 原始细胞 NPM1 FLT3-ITD突变 

分 类 号：R733.71[医药卫生—肿瘤]