Developments in Burkitt's lymphoma: novel cooperations in oncogenic MYC signaling

Spender, L. C. and Inman, G. J. (2014) Developments in Burkitt's lymphoma: novel cooperations in oncogenic MYC signaling. Cancer Management and Research, 6, pp. 27-38. (doi: 10.2147/CMAR.S37745) (PMID:24426788) (PMCID:PMC3890408)

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Burkitt's lymphoma (BL) is an aggressive disorder associated with extremely high rates of cell proliferation tempered by high levels of apoptosis. Despite the high levels of cell death, the net effect is one of rapid tumor growth. The tumor arises within the germinal centers of secondary lymphoid tissues and is identifiable by translocation of the c-MYC gene into the immunoglobulin gene loci, resulting in deregulation of the proto-oncogene. Many of the major players involved in determining the development of BL have been characterized in human BL cell lines or in mouse models of MYC-driven lymphomagenesis. Both systems have been useful so far in characterizing the role of tumor suppressor genes (for example, p53), prosurvival signaling pathways, and members of the B-cell lymphoma-2 family of apoptosis regulators in determining the fate of c-MYC overexpressing B-cells, and ultimately in regulating lymphoma development. Signaling through phosphoinositide (PI)3-kinase stands out as being critical for BL cell survival. Recurrent mutations in ID3 or TCF3 (E2A) that promote signaling through PI3-kinase have recently been identified in human BL samples, and new therapeutic strategies based on coordinately targeting both the prosurvival factor, B-cell lymphoma-XL, and the PI3-kinase/AKT/mammalian target of rapamycin (mTOR) signaling pathway to synergistically induced BL apoptosis have been proposed. Now, engineering both constitutive c-MYC expression and PI3-kinase activity, specifically in murine B-cells undergoing the germinal center reaction, has revealed that there is synergistic cooperation between c-MYC and PI3-kinase during BL development. The resulting tumors phenocopy the human malignancy, and acquire tertiary mutations also present in human tumors. This model may, therefore, prove useful in further studies to identify functionally relevant mutational events necessary for BL pathogenesis. This review discusses these cooperating interactions, the possible influence of BL tumor-associated viruses, and highlights potential new opportunities for therapeutic intervention.

Item Type:Articles
Additional Information:Research performed in our laboratory described in this review was funded by an Association for International Cancer Research Fellowship and by Cancer Research UK.
Glasgow Author(s) Enlighten ID:Inman, Professor Gareth
Authors: Spender, L. C., and Inman, G. J.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:Cancer Management and Research
Publisher:Dove Medical Research
ISSN (Online):1179-1322
Copyright Holders:Copyright © 2014 Spender and Inman
First Published:First published in Cancer Management and Research 6:27-38
Publisher Policy:Reproduced under a Creative Commons License

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