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Burkitt lymphoma

Nature Reviews Disease Primers volume 8, Article number: 78 (2022) Cite this article

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Abstract

Burkitt lymphoma (BL) is an aggressive form of B cell lymphoma that can affect children and adults. The study of BL led to the identification of the first recurrent chromosomal aberration in lymphoma, t(8;14)(q24;q32), and subsequent discovery of the central role of MYC and Epstein–Barr virus (EBV) in tumorigenesis. Most patients with BL are cured with chemotherapy but those with relapsed or refractory disease usually die of lymphoma. Historically, endemic BL, non-endemic sporadic BL and the immunodeficiency-associated BL have been recognized, but differentiation of these epidemiological variants is confounded by the frequency of EBV positivity. Subtyping into EBV+ and EBV− BL might better describe the biological heterogeneity of the disease. Phenotypically resembling germinal centre B cells, all types of BL are characterized by dysregulation of MYC due to enhancer activation via juxtaposition with one of the three immunoglobulin loci. Additional molecular changes commonly affect B cell receptor and sphingosine-1-phosphate signalling, proliferation, survival and SWI–SNF chromatin remodelling. BL is diagnosed on the basis of morphology and high expression of MYC. BL can be effectively treated in children and adolescents with short durations of high dose-intensity multiagent chemotherapy regimens. Adults are more susceptible to toxic effects but are effectively treated with chemotherapy, including modified versions of paediatric regimens. The outcomes in patients with BL are good in high-income countries with low mortality and few late effects, but in low-income and middle-income countries, BL is diagnosed late and is usually treated with less-effective regimens affecting the overall good outcomes in patients with this lymphoma.

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Fig. 1: Burkitt lymphoma incidence and P. falciparum temperature suitability index.
Fig. 2: Multimodal age-specific incidence rates of Burkitt lymphoma.
Fig. 3: Model of Burkitt lymphoma pathogenesis.
Fig. 4: Breakpoints of IGH::MYC translocation in Burkitt lymphoma.
Fig. 5: Involved anatomical sites in Burkitt lymphoma.
Fig. 6: Molecular pathways altered in Burkitt lymphoma.
Fig. 7: Morphology of classic Burkitt lymphoma.
Fig. 8: Risk-adapted treatment approach to Burkitt lymphoma in children, adolescents and adults.

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Acknowledgements

The studies of the authors on Burkitt lymphoma have been supported by the German Ministry of Science and Education (BMBF) in the framework of the ICGC MMML-Seq (01KU1002A-J), ICGC DE-Mining (01KU1505G and 01KU1505E), and MMML-MYC-SYS (036166B) projects and the KinderKrebsInitiative Buchholz Holm-Seppensen. This work was also supported by the BMBF-funded Heidelberg Center for Human Bioinformatics (HD-HuB) within the German Network for Bioinformatics Infrastructure (de.NBI) (031A537A, 031A537C) and by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services contracts HHSN261201100063C and HHSN261201100007I. C.L. is supported by postdoctoral Beatriu de Pinós from Secretaria d’Universitats i Recerca del Departament d’Empresa i Coneixement de la Generalitat de Catalunya and by the Marie Sklodowska-Curie COFUND program from H2020 (2018-BP-00055). B.B. and the NHL-BFM study group are supported by the German Cancer Aid and the Deutsche Kinderkrebsstiftung. The authors thank J. Ferlay of the International Agency for Research on Cancer for assisting with access to data files. The authors thank M. D. Parkin, B. Liu and all of the registries, and members of the African Cancer Registry Network (AFRCN) (http://afcrn.org/index.php/membership/membership-list), for giving them their BL data from Africa for 2018. The authors thank M. Hyer, E. Carver and J. Lyman of Information Management Systems (Rockville, MD) for preparing the files for analysis and drawing the maps.

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Authors and Affiliations

  1. Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain

    Cristina López

  2. Institute of Human Genetics, Ulm University and Ulm University Medical Center, Ulm, Germany

    Cristina López & Reiner Siebert

  3. Non-Hodgkin’s Lymphoma Berlin-Frankfurt-Münster (NHL-BFM) Study Center and Paediatric Hematology, Oncology and BMT, University Hospital Muenster, Muenster, Germany

    Birgit Burkhardt

  4. Department of Pathology, Queen Elizabeth Hospital, Hong Kong SAR, China

    John K. C. Chan

  5. Section of Pathology, Department of Medical Biotechnology, University of Siena, Siena, Italy

    Lorenzo Leoncini

  6. Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, US Department of Health and Human Services, Bethesda, MD, USA

    Sam M. Mbulaiteye

  7. EMBLEM Study, St. Mary’s Hospital, Lacor, Gulu, Uganda

    Martin D. Ogwang

  8. Uganda Cancer Institute, Kampala, Uganda

    Jackson Orem

  9. Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO, USA

    Rosemary Rochford

  10. Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

    Mark Roschewski

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Contributions

Introduction (R.S. and C.L.); Epidemiology (S.M.M. and M.D.O.); Mechanisms/pathophysiology (C.L. and R.R.); Diagnosis, screening and prevention (J.K.C.C., L.L. and S.M.M.); Management (B.B., J.O. and M.R.); Quality of life (B.B., J.O. and M.R.); Outlook (R.S. and C.L.); Overview of the Primer (R.S. and C.L.).

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Correspondence to Reiner Siebert.

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Nature Reviews Disease Primers thanks A. Gloghini, M. A. Piris, L. Sterlin Young and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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López, C., Burkhardt, B., Chan, J.K.C. et al. Burkitt lymphoma. Nat Rev Dis Primers 8, 78 (2022). https://doi.org/10.1038/s41572-022-00404-3

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