The role of ATM mutations and 11q deletions in disease progression in chronic lymphocytic leukemia. Issue 6 (June 2014)

• Record Type: Journal Article
• Authors: Stankovic, Tatjana; Skowronska, Anna
• Is Part Of: Leukemia & lymphoma. Volume 55:Issue 6(2014:Jun.)
• Page Start: 1227
• Page End: 1239
• Publication Date: 2014-06
• Subjects: Leukemia -- Periodicals; Lymphomas -- Periodicals; 616.99419
• DOI: 10.3109/10428194.2013.829919
• Languages: English
• ISSNs: 1042-8194

Abstract

<abstract> <title>Abstract</title> <p> <italic>ATM</italic> gene alteration is a frequent event in pathogenesis of chronic lymphocytic leukemia (CLL) and occurs as monoallelic loss in the form of 11q23 deletion, with and without mutation in the remaining <italic>ATM</italic> allele. <italic>ATM</italic> is a principal DNA damage response gene and biallelic <italic>ATM</italic> alterations lead to ATM functional loss and chemoresistance. The introduction of new therapies, such as intensive chemoimmunotherapy and inhibition of B-cell receptor (BCR) signaling, has changed clinical responses for the majority of CLL tumors including those with 11q deletion, but it remains to be determined whether these strategies can prevent clonal evolution of tumors with biallelic <italic>ATM</italic> alterations. In this review we discuss ATM function and the consequences of its loss during CLL pathogenesis, differences in clinical behavior of tumors with monoallelic and biallelic <italic>ATM</italic> alterations, and we outline possible approaches for targeting the ATM null CLL phenotype.</p> </abstract>