The impact of MYC expression in lymphoma biology: beyond Burkitt lymphoma

Although classically described as the driving oncogene in Burkitt lymphoma (BL), abnormalities of MYC have been recognized in other non-Hodgkin lymphomas as well. For example, MYC is overexpressed in approximately 10% of diffuse large B-cell lymphomas (DLBCL), conferring an adverse prognosis with chemoresistance and shortened survival; only approximately 30% of patients achieve long-term survival despite modern therapies. In contrast to BL, MYC aberrations in DLBCL are usually associated with multiple cytogenetic abnormalities and other genetic lesions, such as concurrent BCL2 translocations. Patients with so-called "double-hit" lymphomas have a worse outcome with few survivors beyond 6 months. It is unclear why MYC translocations are diagnostic in BL but prognostic in other lymphomas; different mechanisms underlying MYC abnormalities and a unique target set of genes may explain some of the variance. Furthermore, MYC possesses nontranscriptional functions other than transcriptional controls on genes regulating cell growth and may also influence the lymphoma microenvironment. Here we summarize current knowledge regarding MYC in lymphomas other than Burkitt lymphoma, with an emphasis on transcriptional, epigenetic, clinical, and microenvironmental consequences.