多重RT-PCR检测儿童急性淋巴细胞白血病融合基因的临床意义

Clinical values of fusion genes detected by multiplex RT-PCR in childhood acute lymphocyte leukemia

目的探讨儿童急性淋巴细胞白血病(ALL)染色体畸变所形成的融合基因与MICM分型及临床诊断、治疗、预后的关系。方法采用多重巢式RT-PCR方法联合染色体核型、免疫表型、临床患儿资料对53例儿童ALL进行研究。结果53例儿童ALL中18例(33·96%)具有11种克隆性基因重排,包括SIL/TAL1D、E2A/PBX1、TEL/AML1、MLLex7/AF9、MLLex8/AF9、MLLex8/AF10、MLLex8/AFX、MLLex9/AF6、MLLex9/ELL、MLLex7/AF4及TLS/ERG。9例患儿有HOX11原癌基因活化。TEL/AML1表达者预后良好;B-ALL合并HOX11活化近期疗效好;T-ALL合并HOX11预后不良;有MLL基因重排的预后极差。结论采用多重RT-PCR方法可快速同时检测儿童急性白血病29染色体畸变所形成的融合基因,完善白血病的MICM分型及指导临床个体化治疗。

Objective To analyse the fusion genes derived from chromosome structural aberrations in children with acute lymphocyte leukemia and the relationship between fusion genes and the MICM types, clinical diagnosis, chemotherapy and prognosis. Methods Bone marrow samples from 53 children with acute lymphocyte leukemia without treatment were analyzed with a multiplex nested RT-PCR. Results Eighteen （33.96%） cases carried 11 types of fusion genes including SIL/TAL1D, E2A/PBX1, TEL/AML1, MLLexT/AF9, MLLex8/AF9, MLLex8/AF10, MLLex8/AFX, MLLex9/ AF6,MLLex9/ELL, MLLex7/AF4 and TLS/ERG from the 53 samples. There were two fusion genes,MLLex7/AF9 and MLLex8/AF9. The activation of oncogene HOX11 was detected in 9 cases. Conclusion The children with TEL/AML1 genes have favourable prognosis, with B-ALL and HOX11 have favourable prognosis at Short term, with T-ALL, HOX11 and MLL gene have the worst prognosis. This multiplex nested RT-PCR reaction could screen 29 types of chromosome structural aberrations at the same time, which may help us to improve classification of the leukemia types of MICM and to direct individulized chemotherapy.