荧光原位杂交技术检测新疆慢性淋巴细胞白血病患者p53基因缺失及其临床意义  

Detection of p53 gene deletion in Xinjiang patients with chronic lymphocytic leukemia by fluorescence in situ hybridization and its clinical significance

作　　者：买买提力·依马木[1] 古再丽努尔·吾甫尔[1] 王晓敏[1] 刘虹[1] 李燕[1] 肖萌[1] 

机构地区：[1]新疆维吾尔自治区人民医院血液科,乌鲁木齐830001

出　　处：《中华医学遗传学杂志》2014年第4期499-503,共5页Chinese Journal of Medical Genetics

摘　　要：目的探讨新疆慢性淋巴细胞白血病（chronic lymphocytic leukemia，CLL）患者临床特征及p53基因缺失的检出率及其临床意义。方法应用荧光原位杂交（fluorescence in situ hybridization，FISH）技术对77例CLL患者进行p53基因缺失的检测，分析p53基因缺失对预后的价值及其与临床特征和部分预后参数的关系。单因素生存分析采用Kaplan-Meier法绘制生存曲线和Log-rank检验。结果（1）77例CLL中，10例（12．9％）检测出p53缺失，而20例对照中均不存在p53缺失，差异有统计学意义（P〈0．05）。其中，32例汉族CLL中4例检测出p53缺失，45例维吾尔族CLL中6例检测出p53缺失，缺失率比较差异无统计学意义（P〉0．05）；p53基因缺失与患者性别、年龄、民族、外周血（除血红蛋白以外）、血清乳酸脱氢酶、β2-微球蛋白及CD38表达水平等无明显相关性（P〉0．05），而与疾病后期及ZAP-70高表达有相关性（P〈0．05）。（2）20例患者接受含氟达拉滨方案治疗，其中p53基因缺失者5例，部份缓解1例，无1例达完全缓解，总缓解率为20％；p53基因无缺失者15例，部份缓解11例，完全缓解4例，总缓解率为75％，二者总缓解率比较差异有统计学意义（P〈0．05）。中位随访39．0（8．0～136．0）个月，死亡11例（14．3％），其中死于CLL及其相关并发症者7例，其他原因者4例。死亡的7例患者均伴有p53基因缺失。伴有p53基因缺失组无进展生存期（18个月）明显短于无p53基因缺失者（55个月），差异有统计学意义（P％0．05）。结论新疆10％以上CLL患者存在p53基因缺失，但维吾尔族和汉族CLL患者p53基因缺失率无差异，p53基因缺失与疾病后期及ZAP-70高表达有关，p53基因缺失者生存期较短，采用含氟达拉滨方案治疗总缓解率低于无缺失者，故应避免选择影响p53信号传导系统的药物。Objective To investigate the presence of p53 gene deletion in Xinjiang patients with chronic lymphocytic leukemia and its clinical significance. Methods Interphase fluorescence in situ hybridization （FISH） was used to detect the p53 gene deletion in 77 patients with CLL. Presence of the deletion and its association with clinical and laboratory features as well as prognostic factors were analyzed. Kaplan-Meier method was used to calculate survivals, and the results were compared using a Log-rank test. Results p53 gene deletion was found in 10 （12.9%） of the patients hut none from the control group （P〈0. 05）. The deletion was found in 12.5% （4/32） of ethnic Hans and 13.3% （6/45） of ethnic Uyghurs （P〉0. 05）. No significant different distribution of p53 gene deletion was found in regard to sex, age, ethnity, peripheral blood cell count （except for Hb） or the levels of lactate dehydrogenase, β2-micro globulin and CD38 （P〉0.05）. The deletion rate was higher in the group with high expression of ZAP-70 and patients with advanced stage disease than that in the group of low expression and early-stage CLL （P〈 0. 05）. Among 20 patients who received fludarabine therapy, the overall remission rate for those with p53 gene deletion （20%） was lower than those without （75%） （P〈0.05）. With a median follow-up time of 39.0 （8.0-136.0） months, 11 cases had died （14.3%）, among them, 7 cases died from CLL and relatedcomplications, and all of them were founded p53 gene deletion. In patients with p53 gene deletion, the progression-free survival （18 months） was shorter than those without the deletion （55 months） （P〈0.05）. Conclusion The p53 gene deletion has been found in more than 10% of patients with CLL, and the deletion rate did not significantly differ between ethnic Han and Uyghur patients. The deletion is associated with advanced stage of the disease. High-level ZAP-70 expression and the presence of p53 deletion are associated with shorter survival and

关 键 词：慢性淋巴细胞白血病 P53基因缺失 预后 

分 类 号：R733.72[医药卫生—肿瘤]