Incidence and clinical implications of ATM aberrations in chronic lymphocytic leukemia.
Incidence and clinical implications of ATM aberrations in chronic lymphocytic leukemia.
复制标题
DOI：
10.1002/gcc.21997
复制
发表时间：
2012-12
影响因子：
3.7
通讯作者：
Malek, Sami N.
中科院分区：
文献类型：
--
作者：
Ouillette, Peter;Li, Jinghui;Shaknovich, Rita;Li, Yifeng;Melnick, Ari;Shedden, Kerby;Malek, Sami N.
A subset of chronic lymphocytic leukemia (CLL) carries mutations in ATM. Such ATM mutations may be particularly relevant in the setting of del11q, which invariably results in the deletion of one ATM allele. To improve our understanding of the frequency and type of ATM mutations that exist in CLL, we resequenced all ATM coding exons in 24 CLL with del11q using direct sequencing. We detected 2 missense mutations, resulting in an ATM mutation frequency of 8%; nonsense and frameshift mutations were not identified. Given the low ATM mutation frequency detected in this cohort, we proceeded with measurements of non-mutational ATM aberrations in CLL through analysis of the activation state of ATM in response to external irradiation. The phosphorylation state of ATM at Ser-1981 was measured using quantitative immunoblotting in purified CLL cells isolated from 251 CLL patients; data were normalized to simultaneous measurements of total ATM protein and actin. Resulting p-ATM/ATM and p-ATM/actin ratios were subsequently analyzed for prognostic significance inclusive and exclusive of TP53 exons 2-10 mutations. From these analyses, conducted in a large prospectively enrolled CLL patient cohort, neither the p-ATM/ATM nor the p-ATM/actin ratios were found to be prognostic for short survival. These data in aggregate demonstrate a low frequency of ATM aberrations in an unselected CLL cohort and do not support a major prognostic role for ATM aberrations in CLL, thus motivating renewed research efforts aimed at understanding the pathobiology of 11q deletions in CLL.
登录
查看更多内容
影响因子：
20.3
作者：
Yuille, MR;Condie, A;Houlston, RS
通讯作者：
Houlston, RS
DOI：
10.1158/1078-0432.ccr-09-2534
发表时间：
2010-02-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Ouillette P;Fossum S;Parkin B;Ding L;Bockenstedt P;Al-Zoubi A;Shedden K;Malek SN
通讯作者：
Malek SN
影响因子：
45.3
作者：
Austen, Belinda;Skowronska, Anna;Stankovic, Tatjana
通讯作者：
Stankovic, Tatjana
DOI：
10.1158/1078-0432.ccr-10-2058
发表时间：
2011-05-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Saiya-Cork K;Collins R;Parkin B;Ouillette P;Kuizon E;Kujawski L;Erba H;Campagnaro E;Shedden K;Kaminski M;Malek SN
通讯作者：
Malek SN
影响因子：
20.3
作者：
Chiorazzi, Nicholas;Ferrarini, Manlio
通讯作者：
Ferrarini, Manlio