Leveraging genomics, transcriptomics and epigenomics to understand chemoimmunotherapy resistance in chronic lymphocytic leukemia.

Patients with chronic lymphocytic leukemia (CLL) have differing clinical outcomes. Recent advances integrating multi-omic data have uncovered molecular subtypes in CLL with different prognostic implications and may allow better prediction of therapy response. While finite-duration chemoimmunotherapy (CIT) has enabled deep responses and prolonged duration of responses in the past, the advent of novel targeted therapy for the treatment of CLL has dramatically changed the therapeutic landscape. In this review, we discuss the latest genomic, transcriptomic, and epigenetic alterations regarded as major drivers of resistance to CIT in CLL. Further advances in genomic medicine will allow for better prediction of response to therapy and provide the basis for rational selection of therapy for long-term remissions with minimal toxicity.