ATM mutation rather than BIRC3 deletion and/or mutation predicts reduced survival in 11q-deleted chronic lymphocytic leukemia: data from the UK LRF CLL4 trial

• Main Authors: Rose-Zerilli, Matthew J. (Author), Forster, Jade (Author), Parker, Helen (Author), Parker, Anton (Author), Rodríguez, Ana E. (Author), Chaplin, Tracy (Author), Gardiner, Anne (Author), Steele, Andrew J. (Author), Collins, A. (Author), Young, Bryan D. (Author), Skowronska, Anna (Author), Catovsky, Daniel (Author), Stankovic, Tanja (Author), Oscier, D.G (Author), Strefford, Jonathan C. (Author)
• Format: Article
• Language: English
• Published: 2014-02-28.
• Subjects: Article
• Online Access: Get fulltext

 ATM mutation and BIRC3 deletion and/or mutation have independently been shown to have prognostic significance in chronic lymphocytic leukemia. However, the relative clinical importance of these abnormalities in patients with a deletion of 11q encompassing the ATM gene has not been established. We screened a cohort of 166 patients enriched for 11q-deletions for ATM mutations and BIRC3 deletion and mutation and determined the overall and progression-free survival among the 133 of these cases treated within the UK LRF CLL4 trial. SNP6.0 profiling demonstrated that BIRC3 deletion occurred in 83% of 11q-deleted cases and always co-existed with ATM deletion. For the first time we have demonstrated that 40% of BIRC3-deleted cases have concomitant deletion and mutation of ATM. While BIRC3 mutations were rare, they exclusively occurred with BIRC3 deletion and a wild-type residual ATM allele. In 11q-deleted cases, we confirmed that ATM mutation was associated with a reduced overall and progression-free survival comparable to that seen with TP53 abnormalities, whereas BIRC3 deletion and/or mutation had no impact on overall and progression-free survival. In conclusion, in 11q-deleted patients treated with first-line chemotherapy, ATM mutation rather than BIRC3 deletion and/or mutation identifies a subgroup with a poorer outcome