p53和ATM基因缺失在慢性淋巴细胞白血病患者中的预后价值

目的 探讨p53和ATM基因缺失在慢性淋巴细胞白血病患者(CLL)中的预后价值.方法 采用间期荧光原位杂交(FISH)技术和p53、ATM基因的序列特异性DNA探针对80例CLL患者的染色体标本进行p53和ATM基因缺失的检测,分析p53和ATM基因缺失与外周血淋巴细胞绝对计数、Binet分期、血清乳酸脱氢酶(LDH)水平、β2微球蛋白(β2-MG)水平、ZAP-70表达、CD38表达、含氟达拉滨治疗疗效之间的相关性,单因素生存分析采用Kaplan-Meier法绘制生存曲线和Log-rank检验,多因素生存分析采用COX多元回归分析.结果 80例CLL患者中14例(17.5%)伴有p53基因缺失,9例(11.3%)伴有ATM基因缺失,其中3例(3.8%)同时伴有p53和ATM基因缺失.p53和ATM基因缺失与患者性别、年龄、Binet分期、外周血淋巴细胞绝对计数、血清LDH及β2-MG、ZAP-70表达水平无明显相关性;CD38高表达组中,p53和ATM基因缺失的发生率均明显高于CD38低表达组,且差异有统计学意义(P=0.025和P=0.001).41例患者接受含氟达拉滨方案治疗,32例不伴有p53和(或)ATM基因缺失的患者中,12例(37.5%)获得完全缓解(CR),9例伴有p53和(或)ATM基因缺失的患者均未获得CR(P=0.047).单因素生存分析显示,伴有p53基因缺失组的生存期明显较不伴有缺失组短,经Log-rank检验差异有统计学意义(P＜0.01);而伴有与不伴有ATM基因缺失组的生存期差异无统计学意义(P=0.556).COX多元回归分析显示,p53基因缺失(P:0.014)和CD38表达水平(P=0.017)是判断CLL预后的独立因素.结论 伴有p53和(或)ATM基因缺失的患者,接受含氟达拉滨方案治疗疗效差,FISH检测p53和ATM基因缺失在CLL预后判断和指导临床治疗中具有重要价值.

Prognostic significance of p53 and ATM gene deletion in patients with chronic lymphocytic leukemia

Objective To explore the prognostic significance of p53 and ATM gene deletion in patients with chronic lymphocytic leukemia(CLL).Methods Interphase fluorescence in situ hybridization (FISH)and probes of LSI p53 and LSI ATM were used to detect p53 and ATM gene deletion in 80 patients with CLL.p53 and ATM gene deletion and their association with some prognostic factors were analyzed.The Kaplan-Meier method was used to calculate survivals,and results were compared using the Log-rank test.Multivariate COX regression analysis was used to assess associations between survival and potential risk factots.Results Out of the 80 CLL patients,p53 gene deletion was found in 14(17.5%)cases,ATM gene deletion in 9(11.3%)cases,and both the two genes delelion in 3(3.8%)cases.There was no significant differences of p53 and ATM gene deletion rates in sex,age,Binet stages,peripheral lymphocyte count,and the levels of LDH,β2-Me,and ZAP-70.The p53 and ATM gene deletion rates were higher in the group of CD38 high expression than that in the group of low expression(P=0.025 and P=0.001).Among 41 patients who received fludarabine containing protocol.none of the nine cases with p53 and/or ATM gene deletion achieved complete response(CR).while 12 of 32(37.5%)cases without the gene deletion achieved CR.The survival time was shorter in patients with p53 gene deletion(P＜0.01).There was no association between outcome and ATM gene deletion(P=0.556).On multivariate analysis by COX regression,p53 gene deletion and CD38 expression(P=0.014 and P=0.017,respectively)were found to be independent faetom in predicting survival.Conclusion CLL patients with p53 and/or ATM gene deletion had poor therapeutic effect,and hence poor prognosis.