Prognostication and Treatment of Burkitt Lymphoma in the Modern Era

Introduction Burkitt lymphoma (BL) is an ultra-aggressive B-cell lymphoma which represents ~1% of adult and ~30% of pediatric lymphomas.1 Apart from the sporadic variant predominant in the United States (US), BL may occur as immunodeficiency-associated or endemic variants. BL is curable in most patients with short-course, dose-intense immunochemotherapy. Molecular underpinning of BL has been well understood, but not yet translated into targeted therapy. About 90% show MYC rearrangement with an immunoglobulin gene (the classical IGH-MYC t(8;14), IGK, or IGL) but otherwise BL has fewer karyotypic abnormalities than other high-grade lymphomas. Commonly mutated genes include the centroblastic transcription factor TCF3 (25%, activating mutations) or its inhibitor ID3 (60%, inactivating mutations), cell cycle regulators CCND3 (30%) and CDKN2A/B (10%), as well as TP53 (35%).2 Of note, tonic PI3K-AKT-mTOR signaling contributes to BL sustained cell survival. The prognostic impact of specific molecular features remains undefined.