Burkitt lymphoma: bridging the gap between advances in molecular biology and therapy

Abstract

Genomic studies have revealed molecular mechanisms involved in the pathogenesis of Burkitt’s lymphoma, including the ID3/TCF3-dependent centroblast gene expression program, tonic PI3K-AKT-mTOR signaling, and deregulation of cell cycle and apoptosis through mutations in cyclin D3, CDKN2A, or TP53. Unfortunately, these advances have not been translated into treatment, which relies on dose-intense cytotoxic chemotherapy. While most patients achieve long-term survival, options for relapsed/refractory disease are lacking, as Burkitt lymphoma is often excluded from clinical trials of novel approaches. The lower-intensity, dose-adjusted EPOCH plus rituximab (DA-EPOCH-R) regimen constitutes a major advance allowing for treatment of older and HIV-positive patients but needs augmentation to better address the central nervous system involvement. Furthermore, DA-EPOCH-R provides a platform for the study of targeted or immunotherapeutic approaches while de-escalating cytotoxic agents and their associated adverse effects. In this review we discuss the epidemiology and molecular genetics of BL, first-line treatment considerations, and potential novel treatment strategies.

Keywords:

• Burkitt lymphoma
• chemotherapy
• immunotherapy
• molecular cytogenetics
• genomics

Disclosure statement

AZ declares no conflict of interest. AJO reports research grants (to the institution) by Genentech/Roche, Spectrum Pharmaceuticals, and TG Therapeutics.

Additional information

Funding

This work was supported by the National Institute of General Medical Sciences at National Institutes of Health under Grant [U54GM115677].