多重RT-PCR检测儿童急性淋巴细胞白血病融合基因及其临床特征分析

The clinical study on children acute lymphoblastic leukemia with different fusion gene by multiplex RT-PCR

目的分析急性淋巴细胞白血病（ALL ）患儿融合基因检测的阳性情况，评估不同融合基因患儿的临床特征及预后差异。 方法回顾性分析2013年7月至2016年12月间四川大学华西第二医院341例采用多重RT－PCR检测融合基因的初发ALL的结果，采用χ2检验和生存分析等方法比较不同融合基因组患儿的临床特征、形态学、免疫分型、细胞遗传学及累积生存率等特点。结果所有ALL患儿的融合基因阳性率为35.2%（120/341），其中TEL－AML1 69例，E2A－PBX1 16例，BCR－ABL 16例，MLL相关基因10例，HOX11L2 5例，SIL－TAL1 4例。不同融合基因组患儿的发病年龄差异有统计学意义（χ2＝29.552，P〈0.05），TEL－AML1和E2A－PBX1多见于≤5岁的患儿；BCR－ABL、MLL相关基因和SIL－TAL1则多见于〉5岁的患儿。BCR－ABL、MLL相关基因及SIL－TAL1阳性患儿初诊时WBC计数较高，且易于出现严重肝脾及淋巴结浸润（χ2＝27.657，45.822，P〈0.05）。不同融合基因组，形态学和免疫分型也存在差异（χ2＝31.333，P〈0.05），TEL－AML1、E2A－PBX1和BCR－ABL主要见于B－ALL，HOX112和SIL－TAL1主要见于T－ALL，而MLL相关基因则在两者中均有表达。生存分析显示，B－ALL患儿BCR－ABL和MLL相关基因的累积生存率明显低于其他基因型（χ2＝15.368，P〈0.05），T－ALL各组的累积生存率无明显差异（χ2＝1.592，P〉0.05）。结论融合基因检测是儿童ALL诊断和疗效监测的重要分子生物学标记，融合基因不同，其临床特征、诊断分型及预后转归具有差异。（中华检验医学杂志，2018, 41：190－195）

ObjectiveTo elevate the prevalence of fusion gene in children with acute lymphoblastic leukemia（ALL）, and compare the difference in the clinical characteristics and prognosis of children with ALL carrying different fusion genes.MethodsThe results of fusion gene that detected by multiplex RT-PCR in children with 341 newly diagnosed ALL between July 2013 and December 2016 in West China Second University Hospital, Sichuan university were retrospectively reviewed. Date of clinical characteristics, morphology, immunophenotype, cytogenetic characteristics and event-free survival were collected and analyzed by χ2 test and survival analysis in different groups according the results of fusion genes.ResultsThe positive rate of fusion genes was 35.2%（120/341）, including 69 cases with TEL-AML1, 16 cases with E2A-PBX1, 16 cases with BCR-ABL, 10 cases with MLL gene rearrangement, 5 cases with HOX11L2 and 4 cases with SIL-TAL1. There was statistical difference in age of different fusion gene groups（χ2=29.552, P〈0.05）, most of children carrying TEL-AML1, E2A-PBX1 were younger than 5 years, but carrying BCR-ABL, MLL gene rearrangement were opposite. The children with BCR-ABL, MLL gene rearrangement or SIL-TAL1 had higher WBC and severer enlarged liver, spleen and lymph node （χ2=27.657, 45.822, P〈0.05）. There also had statistical difference in morphology and immunophenotype in fusion gene groups（χ2=31.333, P〈0.05） . TEL-AML1, E2A-PBX1 and BCR-ABL were mainly found in B-ALL, HOX11L2 and SIL-TAL1 were only found in T-ALL, but MLL gene rearrangement were found in both. The survival analysis showed that the event-free survival （EFS） in groups of BCR-ABL and MLL gene rearrangement were lower than other groups（χ2=15.368, P〈0.05）, but there was no significant difference in T-ALL（χ2=1.592, P〉0.05）.ConclusionsFusion gene detection is an important molecular marker in ALL of children. The ALL children with different fusion genes have different clinical features, immunophenotype and prognosis.（Chin J Lab Med, 2018, 41： 190-195）