Common genomic and transcriptomic signatures in Richter transformation highlight druggable vulnerabilities and guide drug repurposing strategies

Richter transformation (RT) is a rare and aggressive lymphoma occurring in patients with chronic lymphocytic leukemia (CLL). Despite advancements in understanding the pathogenetic mechanisms driving disease transformation, it remains a challenging malignancy. In recent years, multi-center genomic studies have shed light on the heterogeneity of RT, with no single driver alteration identified. This complexity underscores the need for a comprehensive molecular profiling through multi-omic approaches, as one-fits-all therapeutic strategies are unlikely to succeed. Such profiling offers a way to capture actionable vulnerabilities, based on experimental approaches that identify and prioritize “recurrent players” across cohorts.