FISH检测慢性淋巴细胞白血病P53、D13S25、ATM基因缺失及其预后价值  

P53,D13S25,ATM gene deletion in chronic lymphoblastic leukemia detected by fluorescence in situ hybridization and their prognostic significance

作　　者：高银[1] 方鹏[1] 张国平[1] 曹鹏飞[1] 徐雅静[1] 赵谢兰[1] 李晓林[1] 陈方平[1] 

机构地区：[1]中南大学湘雅医院血液科,湖南长沙410008

出　　处：《现代医学》2013年第12期877-881,共5页Modern Medical Journal

基　　金：中南大学研究生学位论文创新基金资助项目(2501-713360010)

摘　　要：目的:研究慢性淋巴细胞白血病(CLL)患者分子遗传学异常情况及其预后价值。方法:采用P53、D13S25、ATM基因序列特异性DNA探针,应用荧光原位杂交(FISH)技术和常规细胞遗传学(CC)方法对75例初治CLL患者进行检测,并分析P53、D13S25、ATM基因缺失与临床指标及FC(氟达拉滨加环磷酰胺)方案化疗疗效之间的相关性。结果:CC结果显示12.8%患者有核型异常,5例未见核分裂相;FISH结果发现58.7%患者有基因异常,其中21.3%伴有P53基因缺失,29.3%伴有D13S25基因缺失,16%伴有ATM基因缺失,8.0%为复杂基因组异常。32例患者接受FC方案化疗,P53基因阴性组与阳性组完全缓解(CR)率分别为48.0%和0(P=0.029);D13S25基因阴性组与阳性组CR率分别为39.1%和33.3%(P=1.000);ATM基因阴性组与阳性组CR率分别为50%和0(P=0.014)。ATM基因缺失与患者血红蛋白水平具有相关性(P=0.019),且易出现广泛淋巴结肿大(P=0.010);而P53、D13S25、ATM基因缺失与其他临床指标如性别、年龄、骨髓及外周血淋巴细胞计数、乳酸脱氢酶(LDH)、β-微球蛋白(β-MG)及Binet分期无明显相关性。结论:FISH较CC更能有效检出CLL患者的分子遗传学异常;FC方案对伴有P53、ATM基因缺失的患者疗效差,而对D13S25缺失患者疗效较好;但FISH检测的分子遗传学异常对CLL患者的预后意义尚需进一步扩大样本数及长期随访观察。Objective： To explore molecular cytogenetic abnormalities in chronic lymphocytic leukemia and its cilinic prognostic significance. Methods： CC and FISH with three probes P53,D13S25,ATM were performed to detect molecular cytogenetic abnormalities in 75 patients with CLL,and the relationship between molecular cytogenetic abnormalities with clinic characteristics and efficacy of FC Chemotherapy was analyzed. Results： Among 75 cases of CLL,only 12. 8% patients were found to have chromosomal abnormalities by CC; whereas 58. 7% patients by FISH,including del（ P53）（ 21. 3%）,del（ D13S25）（ 29. 3%）,del（ ATM）（ 16%）,complex karyotype（ 8%）. Among 32 patients who received FC chemotherapy,the complete remission rate（ CRR） of del（ P53） between negative group and positive group were 48. 0% and 0（ P =0. 029）,del（ D13S25） were 39. 1% and 33. 3%（ P = 1. 000）,del（ ATM） were 50. 0% versus 0（ P = 0. 014）. There was significant correlation between the ATM and the hemogbin level of the patients,in addition,the elevated probability of gaining bulky lymphadenopathy was found in ATM positive patients. However,there was no signifieant differences between P53, D13S25,ATM gene deletion rates and sex,age,peripheral lymphocyte count,the levels of LDH,32-MG,and Binet stages. Conclusion： FISH is a more sensitive technique for detection of genomie aberration in CLL than CC. FC chemotherapy had poor efficacy on CLL patients with P53,ATM gene deletion,while better on patients with del（ D13S25）. A large series study with longterm follow-up is needed to reveal the role of cytogenetic abnormalities in the determination of CLL prognosis.

关 键 词：荧光原位杂交 慢性淋巴细胞白血病 P53基因 D13S25基因 ATM基因 

分 类 号：R733.72[医药卫生—肿瘤]