MLL基因重排急性白血病患儿的临床和生物学特点研究

目的对儿童急性白血病进行混合谱系白血病(mixed lineage leukemia，MLL)基因重排的临床和实验研究：方法应用MLL双色荧光原位杂交(FISH)基因探针进行双色FISH，以13对引物行多重RT—PCR检测融合基冈，并联合染色体R带核型分析及流式细胞仪免疫表型检测，对298例儿童急性白血病中16例含有MLL基因重排患儿进行分析：结果MLL基因重排的白血病在儿童急性白血病中占5.4％，而在婴幼儿白血病中占56．3％；对106例患进行多重RT—PCR，检测到涉及MLL基因重排11例，其中MLL／AF42例，MLL／AF61例，MLL／AF6、MLI／ELL合并MLL／AFX或HOX11各1例，MLL／AF92例，MLL／AF101例，MLI／ELL2例。串联重复dup11q231例，HOX活化1例；27例进行了FISH检测，发现9例有MLL重排，其阳性率为36．0％；16例MLL基因重排患儿中14例(87．5％)有克隆性染色体异常，其中11例累及11号染色体t(4；11)2例，t(6；11)、t(8；11)、t(7；8；11)、t(9；11)各1例， 112例，11q-3例]；16例MLL基因重排患儿中11例为B系ALL，以B祖细胞或前B细胞白血病为主，5例为急性单核细胞白血病，其中3例有CD7和CD2淋系抗原表达；16例MLL基因重排患儿中8例接受治疗，7例获得完全缓解。结论多重RT—PCR和FISH联合是检测MLL重排最精确和灵敏的方法，MLL基冈重排中包括易位、缺失和重复。MLL基因重排的检测对儿童急性白血病预后判断和治疗方案的选择具有重要意义，并且对WHO分型将其单独列为11q23／MLL白血病提供了有力的依据。

Study on clinical and biological characteristics of childhood acute leukemia with MLL gene rearrangements

Objective To study the clinical and laboratory features of childhood acute leukemia(AL) with MLL gene rearrangements. Methods Sixteen of 298 cases of childhood AL with MLL rearrangements were studied by using MLL dual-color FISH, multiplex RT-PCR with 13 pairs of primers in combination with R banding karyotype analysis and cell immunophenotyping by flow cytometry. Results Sixteen cases of childhood AL with MLL rearrangements accounted for 5.4% of 298 AL patients, and 56.3% of infant ALs. Among 106 cases analyzed by multiplex RT-PCR, MLL gene rearrangements were found in 11 cases, including MLL/AF4 fusion gene in 2, MLL/AF6 fusion gene in 1, MLL/AF6 and MLL/ELL combined with MLL/AFX or HOX11 in one case each , MLL/AF9 in 2, MLL/AF10 in 1, MLL/ELL in 2. MLL partial tandem duplication in 1 and activated HOX11 in 1. In 27 cases assayed by FISH, 9 cases (36.0%) were demonstrated MLL gene rearrangements. In 16 patients with MLL gene rearrangements, 14 (87.5%) exhibited clonal chromosome abnormalities involved chromosome 11 in 11 cases: being t(4;11) in 2, t(6;11),t(8;11), (t(7;8;11)), t(9;11) in each trisomy 11 in 2 and 11q- in 3 cases. Among these 16 patients, 11 were B-ALL, and 5 AML-M_5, 3 of the latter were CD7~(+) and CD2~(+). Of these 16 patients, 8 received chemotherapy and 7 of them achieved complete remission, while the other 8 patients gave up treatment. Conclusion Multiplex RT-PCR combined with FISH provided a more accurate and sensitive method for detection of MLL gene rearrangements. Finding out MLL gene rearrangement is of most importance in guiding therapy and predicting prognosis in childhood AL.