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; genomics; immunotherapy; molecular cytogenetics.

Fig. 1.

Molecular mechanisms in Burkitt lymphoma and potential targets for therapy. Prevalence of mutations in specific genes is indicated in circles.

Fig. 2.

The authors’ preferred treatment strategy for Burkitt lymphoma according to risk group and baseline CNS involvement status. ARAC: cytarabine; CNS: central nervous system; IT: intrathecal; LDH: lactate dehydrogenase; MTX: methotrexate; PET: position emission tomography; TLS: tumor lysis syndrome