[慢性淋巴细胞白血病患者中p53和ATM基因缺失的预后意义]

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

作者信息

Xu Wei, Li Jian-yong, Li Li, Wu Yu-jie, Yu Hui, Shen Qiu-dan, Qiu Hong-xia

机构信息

Department of Hematology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing 210029, China.

出版信息

Zhonghua Xue Ye Xue Za Zhi. 2008 Jul;29(7):450-3.

PMID:19035176

Abstract

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 factors.

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 deletion 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, beta2-MG, 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 factors in predicting survival.

CONCLUSION

CLL patients with p53 and/or ATM gene deletion had poor therapeutic effect, and hence poor prognosis.

摘要

目的

探讨p53和ATM基因缺失在慢性淋巴细胞白血病（CLL）患者中的预后意义。

方法

采用间期荧光原位杂交（FISH）技术及LSI p53和LSI ATM探针，检测80例CLL患者的p53和ATM基因缺失情况。分析p53和ATM基因缺失及其与一些预后因素的相关性。采用Kaplan-Meier法计算生存率，并使用Log-rank检验比较结果。采用多因素COX回归分析评估生存率与潜在危险因素之间的关联。

结果

80例CLL患者中，14例（17.5%）存在p53基因缺失，9例（11.3%）存在ATM基因缺失，3例（3.8%）同时存在两种基因缺失。p53和ATM基因缺失率在性别、年龄、Binet分期、外周淋巴细胞计数以及乳酸脱氢酶（LDH）、β2微球蛋白（β2-MG）和ζ链相关蛋白激酶70（ZAP-70）水平方面无显著差异。CD38高表达组的p53和ATM基因缺失率高于低表达组（P=0.025和P=0.001）。在41例接受含氟达拉滨方案治疗的患者中，9例p53和/或ATM基因缺失的患者均未达到完全缓解（CR），而32例（37.5%）无基因缺失的患者中有12例达到CR。p53基因缺失患者的生存时间较短（P<0.01）。结局与ATM基因缺失之间无关联（P=0.556）。通过COX回归进行多因素分析发现，p53基因缺失和CD38表达（分别为P=0.014和P=0.017）是预测生存的独立因素。