The Impact of MYC Rearrangements and "Double Hit" Abnormalities in Diffuse Large B-Cell Lymphoma

Diffuse large B-cell lymphoma (DLBCL) is heterogeneous. Gene expression profiling (GEP) has identified two principal subtypes: germinal center B cell (GCB) and activated B cell (ABC). Most DLBCL cases are distinct from Burkitt lymphoma (BL), but a subset of tumors has a GEP profile between BL and DLBCL, suggesting a spectrum. In parallel, the 2008 World Health Organization (WHO) classification included the category of B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and BL (BCL-U). MYC rearrangement and potential synergy with other genetic aberrations, particularly BCL2 or BCL6, so-called double hit lymphoma, have also been studied in DLBCL and gray zone lymphoma. These subsets have been associated with a poor patient outcome, with the data being strongest for MYC/BCL2 double hit lymphomas. This review summarizes the literature on the impact of MYC rearrangement, as well as MYC/BCL2 double hit, in patients with DLBCL and BCL-U. We also emphasize the evolving nature of these concepts, and outline suggestions for future studies.