The role of ATM mutations and 11q deletions in disease progression in chronic lymphocytic leukemia

Research output: Contribution to journalArticle

Authors

Colleges, School and Institutes

Abstract

Abstract ATM 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 ATM allele. ATM is a principal DNA damage response gene and biallelic ATM 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 ATM 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 ATM alterations, and we outline possible approaches for targeting the ATM null CLL phenotype.

Details

Original languageEnglish
Pages (from-to)1227-39
Number of pages13
JournalLeukemia and Lymphoma
Volume55
Issue number6
Publication statusPublished - Jun 2014

Keywords

  • Ataxia Telangiectasia Mutated Proteins, Chromosome Deletion, Chromosomes, Human, Pair 11, Clonal Evolution, Disease Progression, Humans, Jacobsen Distal 11q Deletion Syndrome, Leukemia, Lymphocytic, Chronic, B-Cell, Molecular Targeted Therapy, Mutation, Phenotype, Prognosis, Tumor Markers, Biological