联合间期和中期荧光原位杂交确定成人急性白血病患者11q23/MLL异常

目的 探讨快速、敏感、有效揭示11q23／MLL基因重排的方法，确定11q23／MLL异常存成人急性白血病（AL）中的发生情况及其临床特征，指导AL风险治疗。方法112例成人AL患者骨髓细胞经24h短期培养按常规方法制备染色体标本，R显带行核型分析；LSIMLL双色分离信号DNA探针行间期荧光原位杂交（FISH）筛选异常信号，有异常信号者行中期FISH确定11q23／MLL基因重排。结果 112例AL患者FISH揭示9例11q23／MLL易位（检出率8．0％），其中常规细胞遗传学分析（CCA）只检出4例（检出率3．6％）。3例CCA示del（11）（q23）者FISH揭示2例为11q23／MLL易位，1例为11号染色体长臂末端缺失。在1例正常核型、1例11q＋和1例无11q23明显异常者，FISH揭示为11q23／MLL易位。除9例易何外，FISH揭示8例存在MLL基因扩增，包括多倍体、均匀染色区（hsr）和双微染色体（dmin）。AL伴11q23／MLL异常者多诊断为B系祖细胞急性淋巴细胞白血病（pro-B ALL）、急性单核细胞白血病（AMoL）或急性双表型白血病（BAL）。结论 使用MLL双色分离信号DNA探针行FISH确定11q23／MLL异常是快速敏感的方法，其检出率高于CCA，有效揭示11q23／MLL易位和扩增。临床诊断pro-B ALL、AMoL或BAL，尤其正常核型者应行FISH以确定11q23／MLL异常。

Combination of interphase- and metaphase-fluorescence in situ hybridization to identify 11q23/MLL abnormalities in acute leukemia patients

Objective To explore a rapid,sensitive and effective method for identifying 11 q23/MLL gene rearrangements and investigate the incidence and clinical features of adult aeute leukemia (AL) patients with 11 q23/MLL abnormalities.Methods Bone marrow samples from 112 adult AL patients were prepared by short-term (24 hours) unstimulated cultme,and karyotyped by R-banding.The abnormal signals were screened by interphase-fluorescence in situ hybridization (FISH) with dual-color break-apart 11q23/MLL- specific probe,and the 11q23/MLL gene rearrangements were determined by metaphase-FISH.Results Of the 112 patients,9 (8.0%) with 11q23/MLL translocations were revealed by FISH,among which only 4 (3.6%) was revealed by CCA.Three patients were reported by CCA to have del( 11 ) (q23 ) ,while by FISH assay two of them were 11q23/MLL translocation and one was true deletion of 11 q23 telemoric terminus.Fur- thermore by FISH assay 11q23/MLL translocations were identified in one each patient with normal karyotype, with 11q+and without overt 11q23 abnormahty.Eight patients with MLL gene amplification including poly- some,homogenous staining region (hsr) and double minute chromosome (dmin)were also disclosed by FISH.AL patients with 11 q23/MLL abnormalities were frequently diagnosed as pro-B acute Iymphoblastic leu- kemia (pro-B ALL) ,acute monocytic leukemia ( AMoL) or biphenotypic acute leukemia (BAL).Conclusion FISH with dual-color break-apart 11q23/MLL-specific probe is a rapid and sensitive method to detect 11q23/MLL abnormalities,as compared with CCA.FISH also effectively discloses translocations and amplifi- cations involving 11q23/MLL,and should be performed in patients diagnosed as pro-B ALL,AMoL or BAL, with CCA normal karyotype.