59例慢性淋巴细胞白血病分子遗传学异常的FISH检测

摘要

目的：探讨间期荧光原位杂交（FISH）技术检测慢性淋巴细胞白血病（CLL）常见分子遗传学异常的意义。方法采用CSF12（12p11．1～12q11．1）、D13S25（13q14．3）、RB1（13q14）、ATM（11q22．3）及p53（17p13．1）等5种探针对59例初诊CLL患者的骨髓细胞进行间期FISH检测，分析上述分子遗传学异常与患者的临床Binet分期、Ria分期及相关实验室检查，包括初诊时外周血淋巴细胞绝对值计数、血红蛋白（Hb）水平、血小板计数（PLT），血清乳酸脱氢酶（LDH）、β2‐微球蛋白（β2‐MG）、CD38和ZAP70水平的相关性。结果59例CLL初诊患者中，存在1种及1种以上分子遗传学异常的有49例，占83．1％。其中，del（13q）34例（69．4％），12号染色体三体（＋12）和p53基因缺失各11例（22．4％），ATM基因缺失5例（10．2％）。各分子遗传学异常与患者临床分期、外周血淋巴细胞计数绝对值、Hb、PLT、LDH、β2‐MG、CD38和ZAP70表达水平之间均无明显相关性（P＞0．05）。≥60岁患者del（13q）异常率（67．6％）显著高于＜60岁患者（40．9％），女性患者p53基因缺失的异常率（35．2％）显著高于男性患者（11．9％），差异均有统计学意义（P＜0．05）。结论FISH技术是检测CLL患者分子遗传学异常快速、准确、敏感的方法，分子遗传学异常与患者初诊时临床表现之间无明显相关性。%Objective To investigate the significance of interphase fluorescence in situ hybridization (FISH ) technology for detecting common molecular cytogenetic abnormalities in the patients with chronic lymphocytic leuke‐mia(CLL) .Methods The bone marrow cells from 59 patients with newly diagnosed CLL were performed the inter‐phase FISH detection by 5 probes ,including CSF12(12p11 .1 -12q11 .1) ,D13S25(13q14 .3) ,RB1(13q14) ,ATM (11q22 .3) and p53(17p13 .1) .Then the correlation between the molecular cytogenetic abnormalities and the clinical Binet staging ,Rai staging and the related laboratory examinations including peripheral blood lymphocyte absolute count ,Hb ,PLT ,LDH ,β2‐MG ,ZAP70 and CD38 levels were analyzed .Results Among 59 cases of newly diagnosed CLL ,49 cases(83 .1% ) had one and more than one kind of molecular cytogenetic aberrations ,in which del(13q) was 34 cases(69 .4% ) ,each of +12 and del(p53) was 11 cases(22 .4% ) and del(ATM ) was 5 cases(10 .2% ) .The mo‐lecular cytogenetic abnormalities had no obvious correlation with the Binet staging ,Rai staging ,peripheral lymphocyte absolute count ,Hb ,PLT ,serum levels of LDH ,β2‐MG ,ZAP70 and CD38(P> 0 .05) .The abnormality rate of del (13q) in the over 60 years old group was significantly higher than that in the less than 60 years old group(P=0 .03) , and the abnormality rate of p53 deletion in female was higher than that in male ,the differences were statistically sig‐nificant(P<0 .05) .Conclusion The FISH technology is a rapid ,accurate and sensitive method in detecting molecular cytogenetic abnormalities in CLL patients ,and there is no significant correlation between molecular cytogenetic ab‐normalities and clinical manifestations in first visiting hospital .