慢性淋巴细胞白血病遗传学异常及临床疗效和预后分析

Cytogenetic abnormalities,clinical curative effect and prognosis of patients with chronic lymphocytic leukemia

目的:探讨应用荧光原位杂交技术(FISH)检测慢性淋巴细胞白血病(CLL)常见染色体异常,并分析其与临床治疗、预后的相关性。方法:对26例初诊CLL患者进行免疫表型及常规细胞遗传学(CC)检测,同时以4种序列特异性探针p53、D13S25、ATM、RB1和1种着丝粒探针CSP12,采用FISH对20例正常对照骨髓建立各探针的检测阈值,然后对26例CLL患者进行检测,检测结果大于阈值为阳性,小于阈值为阴性。结果:所有患者均表达CD19(100%),CD5阳性率为84.6%(22/26),CD23阳性率为65.4%(17/26),CD22阳性率为61.5%(16/26)。CC检测18.5%有核型异常(3/26),FISH检测出20例至少有1种基因异常,依次为D13S25缺失40.0%(8/20),RB1缺失25.0%(5/20),CSP12三体占15.0%(3/20),CSP12单体占5.0%(1/20),p53缺失10.0%(2/20),ATM缺失5.0%(1/20)。18例患者接受了含氟达拉滨的化疗(RF/F/FCR/FC),15例(83.3%)获完全缓解(CR)和部分缓解(PR),4例口服苯丁酸氮芥,4例接受CHOP方案联合化疗,1例获CR,2例PR。结论:FISH技术适用于CLL患者的细胞遗传学分析,提高了CLL遗传学异常检出率,FISH检测结果可为临床治疗方案选择提供一定的理论依据。氟达拉滨治疗方案能明显提高CLL患者长期生存率。

Objective： To investigate the common chromosome abnormalities of patients with chronic lymphocyticleukemia（CLL） by fluorenseence in situ hybridization（FISH） and its correlation with clinical curative effect and prognosis. Methods： Immunophenotypes and conventional cytogenetics （CC） of 26 patients with CLL diagnosed for the first time were examined. Detection threshold values of p53,D13S25, ATM,RB1, and CSP12 probes labelled with flouresence were detemined through examing 20 cases of normal bone marrow by FISH. Twenty--six cases of CLL were examined, and the case was defined to be positive/negative if the detected value was higher/lower than the threshold. Results： The positive rates of CD19, CD5, CD23, CD22 were 100% （26/26）, 84. 6% （22/26）, 65. 4% （17/26）, 61. 5% （16/26） respectively. Through CC method, 18. 5% of patients（3/26） were found to be abnormal karyotype. Through FISH method,at least one kind of gene abnormities was found in 20 patients,40.0% of patients showed D13S25 deletion, 25. 0% of patients showed RB1 deletion, 15. 0% of patients showed CSP12 trisomy deletion, 5. 0% of patients showed CSP12 monomer deletion, 10. 0% of patients showed p53 deletion, 5. 0% of patients showed ATM deletion. A total of 18 patients received fludarabine based chemotherapy （RF/F/FCR/FC）, in which 15 cases （83. 3 %） got complete response （CR） and partialCLL and can improve the detection rate of genetics abnomalities. Clinical treatment schedule can be based on the results of FISH. Fiudarabine-- based chemotherapy schedule can obviously improve long term survival rate of patients with CLL.