Functional and clinical impact of MYC mutations in diffuse large B cell lymphomas

MYC is a transcription factor and an oncogene that drives the pathogenesis of Burkitt lymphomas (BL) and 30–50% of diffuse large B cell lymphomas (DLBCL) (1-3). MYC protein has critical functions that profoundly impact cell fate (reviewed) (4). These include regulation of transcription, translation, metabolism and cell cycle progression (4). Paradoxically, MYC over-expression induces genomic instability and can initiate apoptosis by increasing expression of the tumor suppressor P53 and the pro-apoptotic protein BIM (5). Inactivating P53 or over-expressing the anti-apoptotic protein BCL2 that neutralizes BIM are two effective mechanisms exploited by lymphoma cells to evade MYC-induced apoptosis, leading to unabated cell proliferation and therapeutic resistance (6,7). Mutations in TP53 and the co-expression of MYC and BCL2 proteins are associated with a poor survival in DLBCL patients treated with chemo-immunotherapy (2,3,8). Therefore understanding the mechanisms that deregulate MYC in aggressive lymphomas is clinically important