NPMl基因突变阳性急性髓系白血病的免疫表型与临床特征分析  

The immunophenotypic and clinical characteristics analysis of NPM1 mutated acute myeloid leukemia

作　　者：刘艳荣[1] 常艳[1] 阮国瑞[1] 秦亚溱[1] 赖悦云[1] 石红霞[1] 王亚哲[1] 李玲娣[1] 江滨[1] 李金兰[1] 

机构地区：[1]北京大学人民医院、北京大学血液病研究所,100044

出　　处：《中华血液学杂志》2013年第2期98-103,共6页Chinese Journal of Hematology

摘　　要：目的在形态学亚型比例相似的情况下，比较NPMl基因突变阳性的急性髓系白血病AML（NPMlm^＋ AML）与NPMl基因突变阴性AML（NPMlm^-AML）非特指型（NOS）问的免疫表型与临床特征。方法利用多参数流式细胞术进行免疫分型检测；定量PCR方法检测NPMl基因A、B、D型突变及多种白血病相关基因。NPMlm^＋ AML并进行免疫分型患者104例，NPMlm—AMLNOS患者97例。结果NPMlm^＋ AML与NPM1m^- AMLNOS患者间在女性患者比例、WBC、PLT、骨髓原始细胞比例、正常核型患者比例、WTl基因表达水平、FLT3-ITD突变阳性率和第1疗程诱导缓解率上差异均有统计学意义（P〈0．05）。免疫表型方面主要为早期分化标志CD34、HLA—DR、CDll7、CD38，淋系标志CD4、CD7、CD19、CD2和髓细胞标志CD13、CD14、CD15的低表达，及CDl23、CD33的高表达。其中只有CD34、HLA—DR、CD7和CD4的阳性率在NPM1m^＋AML患者明显低于NPM1m^- AMLNOS患者（P〈0．05），其余均为阳性细胞数的明显不同（P〈0．05）。进一步对NPMlm^＋ AML中M，／M^＋和M^＋／M^＋患者进行分析，结果M^＋／M：患者保留了女性为主及WT1基因表达水平较高的特点（P〈0．05），免疫表型共有10个抗原的阳性细胞数明显不同（P〈0．05），主要为在M^＋／M，中包括单核细胞标志及淋系标志高表达及CD117的低表达。其中HLA—DR、CD64、CD11b、CD10、CD15和CIM6个抗原的阳性率在NPMlm^＋ AMLM^＋ ／M，中也明显高于M^＋／M：患者（P〈0．05）。结论在形态学亚型构成比例相似的情况下，NPM1m^＋ AML与NPM1m^＋—AMLNOS患者相比，其主要临床特征与文献报道的一致。但免疫表型存在明显不同，主要表现为早期祖细胞标志、髓细胞标志和淋系标志的差异。在NPM1m^＋AML中单核细胞相关抗原在M。／M，患者中高表达。Objective To compare the immunophenotypic and clinical characteristics between NPMI mutated acute myeloid leukemia（AML） （NPMlm^＋ AML） and unmutated AML（ NPMlm AML） not other- wise characterized （NOS） under similar FAB subtypes constituent ratio. Methods Immunophenotyping and NPM1 gene mutation type-A,B and D and other leukemic related fusion genes were detected by muhiparamter flow cytometry and real time RT-PCR or PCR,respectively. 104 AML patients with NPMlm^＋ AML and per- formed immunophenotyping assay were included, 97 with NPMlm AML. Results There were significant difference between the two groups at presentation in terms of sex, white blood count （WBC） , platelet counts （PLT） , blast ratio, normal karyotype ratio, WT1 expression level, FLT3-ITD mutation positive rate and remis- sion rate of first course of induction therapy（ P 〈 0.05 ）. On the immunophen0type, the expression of early differentiation antigens （CD34, HLA-DR, CDI17, CD38）, lymphocytic antigens（CD7, CD4, CD19, CD2）, myeloid and monocytic differentiation-associated antigens （CD13, CDI4, CD15） were lower, and that of CD33 as well as CD123 were higher in NPMlm＋ AML patients. Among them, only CD34, HLA-DR, CDT, and CD4 positive cases were significantly lower in NPMlm＋ AML group than in NPMlm AML group （P 〈 0.05）, the rest of them had significant difference in the number of positive cells （ P 〈 0.05 ）. Above features were further analyzed between the M1/M2 and M4/M5 subgroups. M1/M2 cases retained the women prominent and had a higher WT1 expression level（ P 〈 0.05 ）. The expression of monoeytic differentiation-as- sociated antigens including HLA-DR and lymphocytic antigens were higher and that of CD117 were lower in M4/M5 subtype（ P 〈 0.05 ）. Among them, the positive rates of HLA-DR, CD64, CDI 1 b, CD10, CD15, and CD4 were significantly higher in M4/M5 than in M1/M2 in NPMlm ＋ AML group（P 〈 0.05 ）. Conclusion The most clinical characteristics in NPM1 m ＋ AML patients

关 键 词：基因 NPM1 白血病 非淋巴细胞 急性 免疫表型分型 临床特征 

分 类 号：R733.71[医药卫生—肿瘤]