ATM mutations in major stereotyped subsets of chronic lymphocytic leukemia: Enrichment in subset #2 is associated with markedly short telomeres

In chronic lymphocytic leukemia (CLL), antigenic stimulation through the B-cell receptor (BcR) and the accumulation of genetic defects critically affect the natural history of the disease.1 The importance of antigen involvement is underscored by the existence of stereotyped BcR in approximately 30% of CLL cases, where patients belonging to different stereotyped subsets share similar biological profile and clinical course.2,3 ATM defects have been associated with CLL evolution and outcome;4 however, their contribution to the pathobiology of individual subsets has not been explored. Therefore, we decided to use targeted next generation sequencing (NGS) to detect variants in the entire coding region of the ATM gene in well-characterized CLL patients assigned to one of 8 major subsets (#1-8). Since ATM is employed in signaling of telomere erosion, we then investigated the potential correlation between ATM defects and telomere length in selected subsets as well as the clinical impact of these parameters. [...]

• View at Publisher
• View at Scopus