Use

The clinical course of chronic lymphocytic leukemia (CLL) is heterogeneous, ranging from very indolent with a nearly normal life expectancy to rapidly progressive leading to early death. Genomic alterations in genes such as TP53, BIRC3, NOTCH1, and SF3B1, unmutated IgVH, and 17p deletion by FISH are associated with adverse outcomes. These markers improve risk stratification and treatment selection beyond clinical staging. IgVH mutation status (optional add-on) and 17p deletion by FISH are particularly powerful biomarkers. SF3B1 mutations occur in 10-15% of patients and predict shortened time to treatment and poorer survival. NOTCH1 mutations are similarly prognostic. ATM mutations, when combined with 11q deletion, also indicate adverse outcomes. Other mutations in CARD11, CD79B, CXCR4, MYD88, BTK, and PLCG2 relate to resistance and sensitivity to therapies like BTK inhibitors.