应用荧光原位杂交技术检测84例慢性淋巴细胞白血病遗传学异常及预后分析

 摘要 目的：探讨荧光原位杂交 (fluorescence in situ hybridization，FISH) 技术检测慢性淋巴细胞白血病(chronic lymphocytic leukemia，CLL)患者的遗传学异常，并分析与其他预后指标的相关性及预后价值。方法：回顾性分析采用FISH技术进行着丝粒探针CSP12(12p11.1～12q11.1)和序列特异性探针D13s25(13q14.3)、ATM (11q22.3)、RB1(13q14)、p53(17p13.1)检测过的84例CLL患者的临床以及实验室资料。分析FISH技术检测CLL患者中遗传学异常的发生率，并分析遗传学异常与CLL患者年龄、性别、Binet分期、血清乳酸脱氢酶(lactate dehydrogenase，LDH)、CD38表达、生存期之间的相关性。结果：(1)84例CLL患者中，62例有至少有一种遗传学异常。遗传学异常的检出率为73.8%。(2)共发现5种遗传学异常，依次为13q14缺失（56%）、P53缺失（28.6%）、-12（16.7%）、ATM缺失（13.1%）、+12（13.1%）。其中-12为CLL病人中新发现遗传学异常。(3)分析上述5种遗传学异常与年龄、性别、Binet分期、LDH水平、CD38表达的关系，在>60岁年龄病人里，+12阳性率显著高于<60岁病人(24%VS3%, P=0.042)，与性别、Bient分期、LDH水平、CD38表达无关。(4)在LDH增高组中，CD38高表达的病例比例增高（67%VS20%, P=0.015）。(5) 伴有del(17p13)或del(11q22)或复杂异常中位生存时间为75个月，单纯具有del(13q14)异常组的中位生存时间为150个月，其他中位生存时间为120月，但两两比较没有达到统计学差异。结论：(1)FISH技术是一种在分析CLL患者遗传学异常方面较为快速、准确和敏感的方法； (2)CLL病人中除了常见13q14缺失、P53缺失、ATM缺失、+12之外，还可以出现-12异常。

Cytogenetic abnormalities in patients with chronic lymphocytic leukemia and their prognostic significance

Objective To investigate the significance of fluorescence in situ hybridization(FISH) in detecting cytogenetic aberrations in Chinese patients with chronic lymphocytic leukemia(CLL) and explore the characteristics and prognostic significance of cytogenetic aberrations in Chinese patients with CLL.Methods Eighty-four cases of CLL detected by FISH with a panel of probes(CSP12(12p11.1~12q11.1),D13s25(13q14.3),ATM(11q22.3),RB1(13q14),p53(17p13.1)) were retrospectively analyzed by clinical manifestations,laboratory tests and prognosis.Results Cytogenetic aberrations were found in 62 of the 84 CLL patients(73.8%).The most frequent abnormality detected was del(13q14)(56%),followed by del(17p13)(28.6%),del12(16.7%),del(11q22.3)(13.1%),trisomy 12(13.1%).There was no significant relationship among cytogenetic aberrations and sex,Binet stages,level of lactate dehydrogenase,expression of CD38.The proportion of CD38 expression in LDH elevation group was significantly higher than that of LDH normal group.The median survival time with del(17p13),or del(11q22.3) or complex cytogenetic aberrations was 75 months,the median survival time with sole del(13q14) was 150 months,the median survival time with the others was 120 months,but there was no significant deference with each other.Conclusions FISH is a rapid,accurate and sensitive technique for detection of cytogenetic aberration in CLL.The frequencies of the chromosomal abnormalities in Chinese CLL patients are similar to those in Western countries,but the aberration of 12 deletion is a novel discovery.