Genomic Features: Impact on Pathogenesis and Treatment of Chronic Lymphocytic Leukemia

Genomic markers are among the strongest prognostic factors in chronic lymphocytic leukemia (CLL). Chromosomal aberrations, IGHV and TP53 mutation status are well-established and essential to discriminate between a more indolent course of disease and a high-risk CLL, which requires an alternative treatment regimen. In addition, a variety of gene mutations with unclear prognostic value have been identified: SF3B1, ATM, and BIRC3 may describe CLL with adverse outcome, whereas NOTCH1 is predictive for resistance against CD20 antibodies. Integration of novel drivers into a small set of key pathways forms the basis for future pathogenetic and therapeutic implications.