伴有11q23／MLL重排的儿童急性髓系白血病的临床及实验室分析  

Clinical and experimental studies of childhood acute myeloid leukemia with llq23/MLL rearrangements

作　　者：何亚香[1] 薛永权[3] 王红英[1] 邵雪君[1] 潘金兰[3] 徐俊[1] 杨乃超[2] 季正华[1] 黄益萍[1] 胡绍燕[2] 

机构地区：[1]江苏省苏州大学附属儿童医院小儿肿瘤与血液学研究室,215003 [2]江苏省苏州大学附属儿童医院血液科,215003 [3]苏州大学附属第一人民医院、江苏省血液病研究所

出　　处：《中华医学遗传学杂志》2012年第6期677-682,共6页Chinese Journal of Medical Genetics

摘　　要：目的分析伴有11q23／混合谱系白血病（mixed lineage leukemia，MLL）基因重排的儿童急性髓系白血病（acute myeloid leukemia，AML）的临床和实验室特点。方法采用骨髓细胞短期培养法和R显带技术对234例初诊AML患儿进行核型分析；采用逆转录一多重巢式聚合酶链反应（多重PCR）技术检测MLL融合基因以及JlⅥLL部分串联重复；采用双色MLL基因探针，对其中2例核型分析具有11q23易位而多重PCR检测肌L融合基因呈阴性的患儿样本进行间期双色荧光原位杂交（dual-colorfluorescenceinsituhybridization，D-FISH）MLL重排检测。结果R显带提示234例初诊AML患儿中，20例（M514例、M44例、M22例）有涉及11q23的易位，包括t（9；11）（p22；q23）12例，t（1；11）（q21；q23）3例，t（6；11）（q27；q23）2例，t（11；19）（q23；p13）、t（5；11）（q31；q23）和t（X；11）（q24；q23）各1例。多重PCR证实其中18例有MLL的融合转录本，有2例阴性，但D-FISH均检出MLL重排；在其余AMI。患儿的样本中检出8例（M54例、M42例、M2和M6各1例）有MLL部分串联重复。本组AML患儿中，11q23／MLL重排的总检出率11．97％（28／234），其中85．7％（24／28）的病例为M4／M5亚型。本组28例伴有11q23／MLL重排患儿，治疗后完全缓解率为53．8％，与对照组（以同期伴有其他异常核型和正常核型的AML—M4／M5患儿共27例作为对照）的90．5％相比，差异有统计学意义（P〈0．05）。其中2例患儿接受了强烈化疗，分别生存达81和66个月。4例接受了异基因干细胞移植，已分别生存21、20、16和11个月，至今仍在完全缓解中。本组28例伴有11qga／MLL重排患儿的中位生存期为11个月，对照组为15个月，差异无统计学意义（P〉O．05）。结论伴有11q23／MLL重排的AML患儿和单核系白血病高度相关。11q23易位和MLL部分串联重复是相互排斥的，二者预后均较差。�Objective To explore clinical and experimental features of 28 cases of childhood acute myeloid leukemia （AML） with 11q23/MLL gene rearrangements. Methods Karyotypes of 234 cases of de novo childhood AML were analyzed using short-term culture of bone marrow cells and R-banding. The fusion transcripts involving MLL gene and partial tandem duplication of MLL （MLL-PTD） were detected by multiple reverse transcription-polymerase chain reaction （RT-PCR） assay. Two cases with 11q23 translocation by karyotypic analysis but with negative result of multiple RT-PCR were studied with MLL dual-color fluorescence in situ hybridization （D-FISH）. Results R-banding karyotypic analysis has revealed 20 cases with 11q23 translocation （14 cases with M5, 4 cases with M4, 2 cases with M2）, including 12 cases with t（9;11）（p22;q23）, 3 cases with t（1;11）（q21;q23）, 2 cases with t（6;11）（q27;q23）, 1 case with t（11;19）（q23;p13）, 1 witht（5;11）（q31;q23）, and 1 witht（X;11）（q24;q23）. Eighteen cases with 11@3 translocation having fusion transcripts involving MLL genes were confirmed with multiple RT-PCR; 2 cases showed negative results, but they were confirmed to have MLL rearrangements by D-FISH. MLL-PTD wasalso detected in 8 cases （4 cases M5, 2 cases M4, M2 and M6, one case each） from the other childhood AML cases. The total incidence of llq23/MLLgene rearrangements was 11.97% （28/234）, and most of patients （85.7%, 24/28） were M4/M5. The complete remission （CR） rate after treatment for the 28 cases with MLL rearrangements was 53.8%, the difference was significant by statistics （P〈 0. 05） compared with 90.5% for the control group （M4/M5 childhood AML with other karyotypic abnormalities or normal karyotype）. Of them, 2 cases receiving intensive chemotherapy survived for 81 and 66 months, respectively, 4 cases receiving allogeneic stem cell transplantation survived for 21, 20, 16 and 11 months, respectively, and are still alive with CR. The medium survival

关 键 词：单核细胞白血病 染色体核型分析 MLL基因重排 聚合酶链反应 荧光原位杂交 

分 类 号：R733.7[医药卫生—肿瘤]