PMID- 18035414 OWN - NLM STAT- MEDLINE DCOM- 20080805 LR - 20211203 IS - 0145-2126 (Print) IS - 0145-2126 (Linking) VI - 32 IP - 7 DP - 2008 Jul TI - Prognostic significance of ATM and TP53 deletions in Chinese patients with chronic lymphocytic leukemia. PG - 1071-7 AB - Chronic lymphocytic leukemia (CLL) is the most common adult form of leukemia in the Western world, however, infrequent in the Eastern. It shows a remarkable heterogeneity, with some patients having an almost normal lifespan, others surviving only several years after diagnosis despite intensive therapy. To prospectively explore the prognostic significance of ATM and TP53 deletions in Chinese patients with CLL, interphase fluorescence in situ hybridization (FISH) and probes of LSI ATM and LSI p53 were used to detect ATM and TP53 deletions in 95 patients with CLL. ATM and TP53 deletions and their association with some other prognostic factors such as Binet stage, lymphocyte count in peripheral blood, serum lactate dehydrogenase (LDH), beta2-microglobulin (beta2-MG), CD38 and ZAP-70 expressions were analyzed. The Kaplan-Meier method was used to construct survival curves, and results were compared using the log-rank test. Univariate and multivariate Cox regression analyses were used to assess associations between survival time and potential risk factors. Out of the 95 patients with CLL, ATM gene deletion was found in 9 (9.5%) patients, TP53 gene deletion in 16 (16.8%) cases. There were no significant differences between ATM or TP53 deletion and clinical parameters of sex, age, Binet stage, lymphocyte count, LDH, beta2-MG or ZAP-70 expression. However, the frequency of ATM and TP53 deletions were obviously higher in CD38-positive group than in CD38-negative group (P=0.001 and P=0.047, respectively). Among 41 patients received treatment with fludarabine and cyclophosphamide, there were nine patients with TP53 or ATM deletion, and no patient with these cytogenetic abnormalities achieved complete response (CR). Survival analysis showed that the patients with TP53 deletion had significantly shorter survival times than the patients without TP53 deletion. There was no evidence of important association between outcome and ATM gene deletion. Serum levels of LDH and beta2-MG, CD38 expression, and TP53 deletion were the significant factors in determining overall survival (OS). TP53 deletion and CD38 expression were the variables strongly associated with OS by multivariate Cox regression analysis. It was showed that ATM or TP53 deletion is associated with high expression level of CD38 and TP53 deletion as a possible prognostic factor in Chinese patients with CLL. FAU - Xu, Wei AU - Xu W AD - Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, 300 Guangzhou Road, Nanjing 210029, China. FAU - Li, Jian-Yong AU - Li JY FAU - Wu, Yu-Jie AU - Wu YJ FAU - Yu, Hui AU - Yu H FAU - Shen, Qiu-Dan AU - Shen QD FAU - Li, Li AU - Li L FAU - Fan, Lei AU - Fan L FAU - Qiu, Hong-Xia AU - Qiu HX LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20071126 PL - England TA - Leuk Res JT - Leukemia research JID - 7706787 RN - 0 (Cell Cycle Proteins) RN - 0 (DNA-Binding Proteins) RN - 0 (Tumor Suppressor Protein p53) RN - 0 (Tumor Suppressor Proteins) RN - EC 2.7.11.1 (ATM protein, human) RN - EC 2.7.11.1 (Ataxia Telangiectasia Mutated Proteins) RN - EC 2.7.11.1 (Protein Serine-Threonine Kinases) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Ataxia Telangiectasia Mutated Proteins MH - Cell Cycle Proteins/*genetics MH - China MH - DNA-Binding Proteins/*genetics MH - Female MH - *Gene Deletion MH - Humans MH - In Situ Hybridization, Fluorescence MH - Leukemia, Lymphocytic, Chronic, B-Cell/*genetics MH - Male MH - Middle Aged MH - Prognosis MH - Protein Serine-Threonine Kinases/*genetics MH - Tumor Suppressor Protein p53/*genetics MH - Tumor Suppressor Proteins/*genetics EDAT- 2007/11/24 09:00 MHDA- 2008/08/06 09:00 CRDT- 2007/11/24 09:00 PHST- 2007/10/11 00:00 [received] PHST- 2007/10/11 00:00 [revised] PHST- 2007/10/14 00:00 [accepted] PHST- 2007/11/24 09:00 [pubmed] PHST- 2008/08/06 09:00 [medline] PHST- 2007/11/24 09:00 [entrez] AID - S0145-2126(07)00403-1 [pii] AID - 10.1016/j.leukres.2007.10.009 [doi] PST - ppublish SO - Leuk Res. 2008 Jul;32(7):1071-7. doi: 10.1016/j.leukres.2007.10.009. Epub 2007 Nov 26.