Dissecting MYC Influence on mRNA Processing and Protein Translation During Acute Myeloid Leukemia Initiation
Therapeutic options for patients with Acute Myeloid Leukemia (AML) remain limited, and relapse is common. No studies have addressed the cellular and molecular consequences of MYC overexpression and mutations in AML. Through in-vitro and in-vivo experiments in genetically engineered mouse models, we discovered that wild-type and mutant Myc initiate leukemia by regulating translational programs using both transcription-dependent and -independent activities, suggesting that non-canonical MYC functions may represent novel opportunities for therapeutic intervention in MYC-driven cancers. We propose to employ proteomic, ribosome profiling, chromatin immunoprecipitation and RNA sequencing to systematically identify and subsequently target pathways that are dysregulated by oncogenic MYC.