Altered Transcription and Replication Driving MYC-Induced B and T Cell Leukemias

MYC is over-expressed by many cancers, yet its oncogenic mechanisms are incompletely understood. MYC is central to acute lymphoblastic leukemia (ALL) - the most common and second most lethal pediatric malignancy, and ALL afflicts even more adults. Much of MYC's oncogenic function is attributed to its role as a transcription factor, but MYC has been shown to deregulate DNA replication independent of transcription. As master regulator of transcriptomes and epigenomes, we predict that MYC impacts both biologic features in both ALL types, B- and T-ALL. We hypothesize that MYC alters both RNA expression and DNA replication (the ordered spatio-temporal process where genomic domains replicate in either early or late S-phase) in B- and T-ALL, and that these perturbations-some shared, others unique to one ALL type-drive leukemogenesis.