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This finding is of particular relevance given growing reports of RPS15 mutations (including S138F) identified in human Richters Syndrome (RS) characterized by high-grade transformation of CLL to DLBCL 47,48,49 , and stands in stark contrast to prior assumptions that RPS15 is a passenger mutation present in TP53- mutant cells, rather than an independent driver of RS

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Polypharmacology-based integrated systems biology approaches along with computational modeling, pharmacological, and clinical studies are productive for identification of novel molecular determinants essential in drug discovery and development