常见白血病融合基因筛查在白血病诊断与分型中的意义  

Role of molecular screening for common fusion genes in the diagnosis and classification of leukemia

作　　者：祝毓琳[1] 张英[1] 朱平[1] 杨英[1] 杜金伟[1] 刘静[1] 

机构地区：[1]北京大学第一医院血液内科,北京100034

出　　处：《北京大学学报（医学版）》2005年第3期236-239,共4页Journal of Peking University:Health Sciences

基　　金：国家自然科学基金(30470739);教育部博士学科点专项基金(20040001017)资助~~

摘　　要：目的: 分析病人白血病细胞染色体畸变涉及的86种融合基因和临床白血病类型的相关性,探讨常见融合基因筛查法在临床诊断和分型中的应用价值。方法: 收集161例初发或者复发的白血病患者及8例骨髓增生异常综合征(MDS)患者的骨髓细胞,提取RNA,用32条特异性引物逆转录为cDNA,利用白血病29种染色体畸变形成的融合基因的86种mRNA剪接变异体引物,分8管进行多重RT PCR,筛查白血病融合基因。结合临床状态和形态学观察了解融合基因与白血病类型的关系。结果: 白血病中115例(71% )分别检测出10种白血病常见融合基因,包括AML1 /ETO、PML/RARα、PLZF/RARα、dupMLL、MLL/AF6、MLL/AF10、CBFβ/MYH11、BCR/ABL、Hox11、Evi1。其中52例慢性粒细胞白血病(CML)100%检出BCR/ABL; 25例急性早幼粒细胞白血病(APL)中88%检出融合基因,其中21例APL检测出PML/RARα, 1例APL检测出PLZF/RARα; AML1 /ETO阳性的17例急性白血病(AL)16例为FAB M2亚型, 1例为混合型白血病; CBFβ/MYH11阳性的4例AL3例为FAB分型的M4, 1例为M5,属于向粒单细胞系统分化的白血病。16例AL检测出MLL基因异常,其中MLL/AF6白血病均为FAB分型的M5,具有典型的原始单核细胞白血病的特征。17例急性淋巴细胞白血病(ALL) 5例检测出BCR/ABL。8例MDS病人中2例检测出融?Objective: To assess the value of common fusion genes analysis in the diagnosis and classification of leukemia by multiplex RT-PCR. Methods:The multiplex RT-PCR, including 8 parallel PCR reactions, could screen 86 mRNA breakpoints or splice variants at the same time, which was important for the diagnosis and prognosis of leukemia. Bone marrow samples from 161 cases of leukemia and 8 cases of myelodysplastic syndrome (MDS) were involved in the study. The distribution of common fusion genes in leukemia was analyzed by the method mentioned above in combination with clinical and morphologyical features. Results: Ten fusion genes were detected in 115 cases of leukemia, including AML1/ETO,PML/RARα,PLZF/RARα,dupMLL,MLL/AF6,MLL/AF10,CBFβ/MYH11,BCR/ABL,Hox11,and EVI1 BCR/ABL was positive in all the 52 cases of chronic myeloid leukemia; PML/RARα was found in 21 of 25 acute promyelocytic leukemia(APL), and PLZF/RARα was detected in one case of APL. Sixteen cases of 17 AML1/ETO-positive acute leukemia (AL) belonged to FAB-M2 subtype, and one case was mixed leukemia.Three of 4 AL cases carrying CBFβ/MYH11 were M4 subtype, and one was M5 subtype. MLL aberrations were found in 16 AL, in which all MLL/AF6 translocation existed in M5 subtype with classic monoblastic characters. Furthermore, BCR/ABL was detected in 5 acute lymphoblastic leukemia (ALL) cases. Fusion genes were also found in 2 MDS cases, of which AML1/ETO positive-MDS-RAEB progressed to AML rapidly. Conclusion:Screening of common fusion genes by multiplex RT-PCR is an important tool which could provide useful and reliable molecular genetic information for the diagnosis and treatment of leukemia.

关 键 词：白血病诊断 骨髓增生异常综合征(MDS) PML/RARΑ BCR/ABL 急性早幼粒细胞白血病 急性淋巴细胞白血病 慢性粒细胞白血病 融合基因 单核细胞白血病 基因筛查法 FAB分型 人白血病细胞 RT-PCR PLZF 染色体畸变 白血病患者 

分 类 号：R733.7[医药卫生—肿瘤] R446.11[医药卫生—临床医学]