In 2016, the World Health Organization designated double-hit lymphoma (DHL) as a category of B-cell non-Hodgkin lymphoma (NHL). DHL is genetically characterized by rearrangements within 2 genes, MYC and BCL-2 or, less commonly, BCL-6.1,2
DHL shares some similarities with 2 other aggressive forms of lymphoma: diffuse large B-cell lymphoma (DLBCL), which tends to have BCL-2 or BCL-6 mutations and is the most common type of NHL worldwide, and Burkitt lymphoma, which is characterized by MYC mutations. However, DHL also differs from these 2 lymphoma subtypes, and accurate diagnosis is important for treatment decisions.1–3
In a review published in Expert Review of Hematology, Lin-Rong Li, of the Southern Medical University in China, and colleagues discussed traditional and novel therapies for patients with DHL. They also highlighted the move in DHL treatment toward precision medicine facilitated by high throughput DNA sequencing.1
“DHL represents a relatively small population of diffuse large B-cell lymphomas or total lymphomas,” said coauthor Liang Wang, MD, of the department of hematology at Zhujiang Hospital of Southern Medical University in China, in an interview with Hematology Advisor.
Approximately 7.9% of DLBCLs and between 32% and 78% of Burkitt lymphomas have rearrangements in MYC and BCL-2/BCL-6.4 One mechanism for lymphomagenesis in these cases is the synergistic upregulation of the MYC proto-oncogene and BCL-2, an apoptosis inhibitor.1
“DHL cases generally have concurrent MYC and BCL-2 breakpoints. These breakpoints are known to contribute to the aggressive course and chemotherapy resistance,” said Dr Wang.