Burkitt Lymphoma Pathogenesis and Therapeutic Targets from Structural and Functional Genomics
| Autor: | James R. Cook, Hans Konrad Müller-Hermelink, Erlend B. Smeland, German Ott, George E. Wright, Louis M. Staudt, Roland Schmitz, Sam M. Mbulaiteye, Stefania Pittaluga, Yandan Yang, Sameer Jhavar, Richard I. Fisher, Thomas A. Waldmann, Randy D. Gascoyne, Arthur L. Shaffer, Steven J. Reynolds, Dennis D. Weisenburger, Elias Campo, Meili Zhang, Lisa M. Rimsza, Eric Buras, Michele Ceribelli, Wenming Xiao, Alan B. Rickinson, Ryan M. Young, Wyndham H. Wilson, Martin Rowe, Elaine S. Jaffe, Xuelu Liu, Holger Kohlhammer, Andreas Rosenwald, Joseph M. Connors, Philip M. Kluin, Raymond R. Tubbs, Wing C. Chan, Jan Delabie, Weihong Xu, Daniel J. Hodson, Martin D. Ogwang, Rita M. Braziel, Hong Zhao, John Powell |
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| Přispěvatelé: | Stem Cell Aging Leukemia and Lymphoma (SALL) |
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
PROTEINS
Genes myc Receptors Antigen B-Cell Article REGION Phosphatidylinositol 3-Kinases RNA interference medicine Basic Helix-Loop-Helix Transcription Factors Humans Molecular Targeted Therapy Cyclin D3 B-cell lymphoma Transcription factor B cell Multidisciplinary biology Cell Cycle B-CELL LYMPHOMA High-Throughput Nucleotide Sequencing Cyclin-Dependent Kinase 6 Genomics Cell cycle medicine.disease Burkitt Lymphoma Lymphoma Neoplasm Proteins medicine.anatomical_structure IMMUNOGLOBULIN Cancer research biology.protein Inhibitor of Differentiation Proteins RNA Interference Cyclin-dependent kinase 6 Signal Transduction |
| Zdroj: | Nature, 490(7418), 116-120. Nature Publishing Group |
| ISSN: | 0028-0836 |
| Popis: | Burkitt's lymphoma (BL) can often be cured by intensive chemotherapy, but the toxicity of such therapy precludes its use in the elderly and in patients with endemic BL in developing countries, necessitating new strategies(1). The normal germinal centre B cell is the presumed cell of origin for both BL and diffuse large B-cell lymphoma (DLBCL), yet gene expression analysis suggests that these malignancies may use different oncogenic pathways(2). BL is subdivided into a sporadic subtype that is diagnosed in developed countries, the Epstein-Barr-virus-associated endemic subtype, and an HIV-associated subtype, but it is unclear whether these subtypes use similar or divergent oncogenic mechanisms. Here we used high-throughput RNA sequencing and RNA interference screening to discover essential regulatory pathways in BL that cooperate with MYC, the defining oncogene of this cancer. In 70% of sporadic BL cases, mutations affecting the transcription factor TCF3 (E2A) or its negative regulator ID3 fostered TCF3 dependency. TCF3 activated the pro-survival phosphatidylinositol-3-OH kinase pathway in BL, in part by augmenting tonic B-cell receptor signalling. In 38% of sporadic BL cases, oncogenic CCND3 mutations produced highly stable cyclin D3 isoforms that drive cell cycle progression. These findings suggest opportunities to improve therapy for patients with BL. |
| Databáze: | OpenAIRE |
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