儿童急性淋巴细胞白血病TEL基因微卫星和杂合性缺失检测的临床意义

目的检测12号染色体TEL基因微卫星不稳定性(MSI)和杂合性缺失(LOH),与儿童急性淋巴细胞白血病发生、发展及预后的关系。方法采用多重PCR、聚丙烯酰胺凝胶电泳及银染技术检测了12号染色体上TEL基因附近的4个微卫星位点(D12s89、D12s98、D12s269、D12s358)的MSI和LOH发生情况,并对其中的18例病人进行了初诊、缓解和复发三期MSI和LOH的检测。结果53例ALL儿童MSI和LOH总的发生率分别为3·77%(2/53)和43·40%(23/53),其中D12s89位点LOH的发生率最高为39·62%(21/53),D12S269位点LOH的发生率最低为9·43%(5/53)(χ2=5·24,P<0·01);动态检测其中的18例患儿,初诊期LOH的发生率为61·11%(11/18),缓解期为11·11%(2/18),复发期为66·67%(12/18),初诊和复发期各位点LOH的发生率明显高于缓解期(χ2=8·88,11·69,P<0·01);3例初诊未检测出LOH的患者,复发期3位点同时检测到LOH;2例患者在初诊、缓解和复发三期均检测到LOH。5例正常对照和15例良性血液病对照均未检测到LOH及MSI的发生。结论TEL基因与儿童ALL的发生、发展有关,微卫星不稳定性的检测可用于白血病的诊断及预后判断,并可作为临床上微小残留白血病的检测方法之一。

Clinical significance of the measurement of microsatellite instability of TEL gene in childhood acute lymphoblastic leukemia

Objective To find out the correlation between TEL gene and the occurrence, progression and prognosis of children acute lymphoblastic leukemia (ALL), we carry out a study on microsatellite instability (MSI) and loss of heterozygosity (LOH) linked to TEL gene on chromosome 12. MethodsMSI and LOH in 53 cases of children ALL, 15 cases of benign hematopathies and 5 cases of normal children were detected by multiplex-PCR amplification at 4 microsatellites linked to TEL gene on chromosome 12, gel electrophoresis and argentine dye. Results we detected LOH in 23 cases out of 53 children ALL, the frequency of LOH on 4 microsatellites (D12s89, D12s98, D12s269, D12s358) was 43.40% (23/53), among those microsatellites, the expression ratio of LOH on D12s89 was the highest 39.62%(21/53). There was 2 cases detected MSI on D12s89, D12s98, D12s269 respectively, its frequency was 3.77% (2/53) . At the same time, LOH and MSI were dynamic observed in the three stages (beginning, remission, relapse) of 18 cases of all the patients, the frequency of LOH in the three stages was 61.11%(11/18), 11.11%(2/18) and 66.67%(12/18) respectively (χ2=8.88, 11.69, P<0.01 ). 3 cases were not found LOH and MSI in the beginning stage, but LOH was found simultaneously in 3 loci in the relapse stage. LOH were consistently detected in the three stages of 2 cases. LOH and MSI were not found on those four sites in 15 cases of benign hematopathies and 5 healthy children. Conclusion There was a correlation between TEL gene and the initiation, development of childhood ALL. The detection of MSI play an important role in the diagnosis and prognosis of leukemia, as well as the detection of minimal residual leukemia.