儿童急性淋巴细胞白血病常见融合基因的检测及意义

Fusion genes in childhood acute lymphoblastic leukemia and its clinical significance

目的建立逆转录-巢式PCR检测融合基因的方法,检测4种常见融合基因在儿童急性淋巴细胞白血病中阳性率,并对阳性患儿进行初步临床资料分析。方法对收治的92例初发的急性淋巴细胞白血病(ALL)患儿,于化疗开始前抽取骨髓标本1.5～2.0 ml,采用巢式RT-PCR方法检测最常见的4种融合基因:TEL/AML1、E2A/PBX1、m-BCR/ABL和AF4/MLL。结果92例ALL患儿中TEL/AML1阳性21例,阳性率22.8%,占B细胞性ALL的24.7%(20/81例);6例E2A/PBX1阳性(6.5%),在前B细胞性ALL中占20.0%(3/15例);2例AF4/MLL阳性(2.2%),在婴儿ALL中占33.3%(2/6例);仅检测到1例m-BCR/ABL阳性(1.1%)。结论巢式RT-PCR方法是检测融合基因有效、敏感的方法。TEL/AML1在儿童ALL中阳性率最高,尤其是在B细胞性ALL中,该融合基因阳性的患儿病情较轻。

Objectives To establish reverse transcription and nest polymerase chain reaction method to detect expression of four fusion genes in childhood acute lymphoblastic leukemia （ALL）, and analyze the clinical characters of the patients with positive fusion genes. Methods Reverse transcription and nest polymerase chain reaction procedure was set up and four of the most frequent fusion genes in pediatric ALL, such as TEL/AML1, E2A/PBX1, m-BCR/ ABL and AF4/MLL fusion transcripts were examined in bone marrow from 92 newly diagnosed childhood ALL patients. Results TEL-AML1 fusion gene was found in 21 out of 92 cases, accounting for 24.7% in childhood B lineage ALL patients. No statistical difference was found in age, complete remission （CR） rate within 15 days and early death rate between the positive and negative TEL/AML ALL patients, while the initial WBC count was lower in positive cases. The incidence of E2A/PBX1 fusion gene was 6.5% in childhood ALL （6/92）. Only one case with positive m-BCR/ABL fusion gene was detected （1.1%） . Moreover, two patients with positive AF4/MLL were found among 6 cases of infant ALL （33.3%）. Conclusions Compared with RT-PCR, nested RT-PCR technology is more specific and sensitive to detect fusion genes as targets for molecular classification of childhood ALL at diagnosis. TEL/AML1 fusion gene is the most common molecular aberration in childhood ALL, and positive patients show lower peripheral tumor load at diag- nosis. Both TEL/AML1 and E2A/PBX1 fusion transcripts are the most frequently occurred in pediatric B lineage ALL.