急性白血病11q23/MLL基因易位重排及其临床意义

目的：研究11q23/MLL基因易位重排在急性白血病（AL）中的发生率、产生融合基因的常见类型及其临床意义.方法：用荧光原位杂交技术，MLL双色断裂分离重排探针检测50例AL患者（49例初治，1例难治）的11q23/MLL基因，用流式细胞仪检测免疫表型，对于11q23/MLL基因易位重排阳性的患者，用巢式RTPCR方法检测11q23/MLL基因易位重排形成的6种常见融合基因类型.结果：6例AL有11q23/MLL基因易位重排，发生率为12%，2例为AML-M5，4例为ALL且均为B-ALL.2例11q23/MLL基因易位重排阳性的AML M5患者融合基因均为MLL/AF9，其中1例为初治，发病时左侧小腿有白血病细胞浸润，本例患者化疗1疗程获CR;1例为难治性AL患者，于第3个疗程化疗后才达CR.4例11q23/MLL基因易位重排阳性的B-ALL患者中有2例于诊断后3周内死于全身衰竭和感染，化疗未获CR，其中1例患者的融合基因为MLL/ENL，1例未扩出融合基因产物;1例于诊断后第2天因DIC脑出血死亡，未进行化疗，其融合基因为MLL/AF9;1例发病时胸椎有白血病细胞浸润，1疗程化疗后获CR，其融合基因产物未扩出.结论：荧光原位杂交技术是检测AL11q23/MLL基因易位重排快速、灵敏的方法，巢式RT-PCR是检测11q23/MLL基因易位重排所产生的融合基因类型简便可行的方法;有11q23/MLL基因易位重排的AL患者临床症状凶险，预后差。

Laboratory detection and clinical significance of translocation rearrangements of 11q23/MLL gene in acute leukaemias

Objective:To study the incidence, frequent types of fusion genes and clinical significance of translocation rearrangements of 11q23/MLL gene in acute leukaemias.Method:Translocation rearrangements of 11q23/MLL gene in acute leukaemias were detected by fluorescence in situ hybridization(FISH) with MLL dual colour break apart probe, immunophenotypes were detected by flow cytometry, and 6 frequent types of fusion genes resulting from translocation rearrangements of 11q23/MLL gene were detected by nested RT-PCR.Result:6 of 49 de novo and 1 non-remission acute leukaemia patients had translocation rearrangements of 11q23/MLL gene, which incidence was 12%, 2 patients were diagnosed ANLL-M_5, 4 were diagnosed B-ALL. The fusion genes of the 2 ANLL-M_5 patients who had translocation rearrangements of 11q23/MLL gene was MLL/AF9 of the two patients, one of them was de novo acute leukaemia, whose left leg had been infiltrated by leukaemia cells when she was diagnosed acute leukaemia. This patient got CR after 1 course of chemotherapy. The other was non-remission acute leukaemia patient, he got CR after 3 courses of chemotherapy. 2 of the 4 B-ALL patients had translocation rearrangements of 11q23/MLL gene died of system failure and infection in 3 weeks after diagnosis, they didn't get CR by chemotherapy. As for their fusion genes, one of them was detected MLL/AF9, the other's fusion gene was not detected. The third patient died of DIC with cerebral hemorrhage, his chemotherapy was not carried up and his fusion gene was detected MLL/AF9. One patieat's brustwirbel had been infiltrated by leakemia cells when diagnosed and got CR after chemotherapy, the fusion gene was not detectecl etiher.Conclusion:FISH is a fast and sensitive mathod to detect translocation rearrangements of 11q23/MLL gene in acute leukaemias and nested RT-PCR is a convenient and feasible mathod to detect the fusion genes resulting from translocation rearrangements of 11q23/ MLL gene. Acute leukaemia patients with translocation rearrangements of 11q23/MLL gene have hazardous clinical symptoms and worse prognosis.