t(12;21)儿童急性淋巴细胞白血病的研究

Study of the childhood acute lymphoblastic leukemia with t(12;21)

目的 研究t(12 ;2 1)儿童急性淋巴细胞白血病 (ALL)的临床与预后特征。方法 应用常规核型分析 (CCA)、双色间期荧光原位杂交 (I FISH)和RT PCR技术 ,对 5 1例ALL患儿骨髓或外周血有核细胞进行t(12 ;2 1)和TEL AML1融合基因检测。结果 11例患儿存在t(12 ;2 1) ,占儿童初治ALL的2 1.6 % ,占非T细胞系ALL的 2 6 .9% (41例中 11例 ) ;中位发病年龄 6 .8岁 (2 .9～ 12 .0岁 ) ;非T细胞系免疫表型 ,以普通型ALL为主 ,不伴髓系抗原高表达 ;CCA检测核型多正常 ,仅 1例有t(12 ;2 1) ;72 7%的患儿伴TEL等位基因缺失。与其他儿童非T细胞系ALL相比 ,t(12 ;2 1)患儿的血小板计数和IgH重排发生率低 ;男女性别比、初诊时贫血、出血、器官肿大程度、白细胞计数和完全缓解 (CR)率、4周内达CR比例、持续CR时间及复发率未见显著差异。结论 t(12 ;2 1)是我国儿童ALL最常见的染色体易位。为非T细胞系免疫表型 ,以普通型ALL为主 ,多伴TEL等位基因丢失。临床表现和近期疗效与其他非T细胞系儿童ALL无显著差异。与国外报道相比 ,患儿的发病年龄偏大 ,血小板计数和IgH重排率低 ,核型多为正常。

Objective To explore the incidence,clinical characteristics and prognosis of childhood acute lymphoblastic leukemia (ALL) with t(12;21). Methods t(12;21)/TEL-AML1 fusion gene was examined in bone marrow or peripheral blood mononuclear cells from 51 newly diagnosed childhood ALL patients by conventional cytogenetic R-banding analysis (CCA),dual colour interphase fluorescence in situ hybridization (I-FISH),and nested reverse transcriptase-polymerase chain reaction (RT-PCR). Results t(12; 21)/TEL-AML1 fusion gene was found in 11 cases by FISH or PCR,accounting for 21.6% and 26.9% in childhood ALLs and in non-T lineage ALL cases,respectively. The median age at diagnosis was 6.8 (2.9 to 12) years. All of the t(12;21) patients expressed non-T lineage immunophenotype,and most of them were common-ALL. High myeloid antigen coexpression was not found. In 11 CCA cases,normal karyotype was found in 7,and a dubious t(12;21) in one. TEL allele deletion was found in 8 (72.7%) of t(12;21) positive cases by FISH. By comparison,no statistic difference was found in sex,anemia,hemorrhage,organ enlargement,and initial WBC count between the positive and negative non-T lineage ALLs,but the platelet count and the frequency of IgH gene rearrangement were much lower in positive cases (P =0.008 and 0.007,respectively). Moreover,no difference was found in overall CR rate,CR rate within 4 weeks,CR duration and relapse rate between the two groups. Conclusion t(12;21) was the most common chromosomal translocation in childhood ALL,but not all of them could be detected by CCA. t(12;21) cases showed non-T cell immunotypes,most of them were CD_ 10 + ALL. TEL allele deletion was common in these cases. There was no significant difference in clinical characteristics and short term outcome between the t(12;21) and the TEL-AML1 negative cases. In our data,Chinese t(12;21) ALL showed older in age,lower BPC,lower IgH rearrangement frequency and more of normal karyotype as compared with the reports abroad.