核型正常的NPM1突变阳性的急性髓系白血病的免疫表型与临床特征分析

本研究在形态学亚型构成比例相似情况下比较具有正常核型的NPM1基因突变阳性的AML（NPM1m＋AML）与突变阴性的AML（NPM1m-AML）非特指型（NOS）间的免疫表型、临床、细胞遗传学和基因表达特征。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NPM1 基因A、B、D型突变及多种基因；正常核型的NPM1m＋AML并进行免疫分型患者共77例，AMLNOS患者55例。结果表明：NPM1m＋AML患者以女性为主，WBC和血小板计数、聊表达水平、FLT3一ITD突变阳性率和第一疗程诱导缓解率明显高于NPM1m—AML（P〈0．05）。在免疫表型方面共有10个抗原显著不同，主要为早期分化标志CD34、HLA—DR、CD117、CD38和淋系标志CIM、CD7、CDl9、CD2的低表达及CDl23、CD33的高表达。进一步分析NPM1m＋AML中M1／2和M4／5患者的结果显示，M1/2患者保留了女性为主及WBC数和形丌表达较高的特点（P〈0．05），免疫表型共有9个抗原的阳性细胞数明显不同（P〈0．05），主要为包括HLA-DR内的单核细胞标志及CD7在M4/5中高表达及CD117的低表达。结论：在形态学亚型构成比例相似及正常核型情况下，NPM1m＋AML高表达聊，且具有较高的CR率，免疫表型主要表现为早期祖细胞标志、淋系标志的低表达和CD33、CD123的高表达。在NPM1m＋AML中只有M4/5患者高表达单核细胞相关标志。

Immunophenotypic and Clinical Characteristic Analysis of NPMI Mutated Acute Myeloid Leukemia with a Normal Karyotype

This study was purposed to compare the immunophenotypic and clinical characteristics of NPM1 mutated acute myeloid leukemia with a normal karyotype under the similar constituent ratio of FAB subtypes. Immunophenoty- ping and NPM1 gene mutation type-A,B and D and other leukemic related fusion genes were detected by multiparamter flow cytometry and real time RT-PCR or PCR,respectively. 77 AML patients with a normal karyotype（NK） and muta- ted NPM1 gene（NPM1m＋ AML） detected by immunophenotyping assay were included in this study. 55 cases without NPM1 mutation（NPM1m-AML） and with normal karyotype were served as negative control. The results showed that there was significant difference between NPM1m＋ AML and NPM1m-AML in terms of sex, white blood count, platelet counts,blast, WT1 expression level,FLT3-ITD mutation positive rate and response to treatment. The characteristic immu- nophenotype is lower expression of early differentiation-associated antigens （ CD34, HLA-DR, CD117, CD38 ）, lympho- cytic antigens （ CD7, CD4, CD19, CD2） and higher expression of CD33 and CD123 （ P 〈 0.05 ）. When above features was further analyzed between the M1/2 and M4/5 subgroups in NPM1m＋ AML patients, the M1/2 cases retained a higher frequency in women and a higher WT1 expression level（ P 〈 0.05 ）. Monocytic differentiation-associated antigens inclu- ding HLA-DR and lymphocytic antigens CD7 were higher expressed and CD117 was lower expressed in M4/5 subgroup（ P 〈 0.05 ）. It is concluded that under condition of similar constituent ratio of M1/2 and M4/5 subtype and normal karyotype, NPM1m＋ AML patients have higher WT1 expression level and better response to treatment. The major immunophenoty- peic features of NPM1m~ AML patients are lower expression of early differentiation antigens and lymphoid lineage anti-gens and higher expression of CD33 and CD123. Monocytic differentiation-associated antigens only higher are expressed in M4/5 cases when compared with M1/2 cases within NPM1m ＋ AML patients.