Journal
ONCOGENE
Volume 29, Issue 6, Pages 888-897Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/onc.2009.377
Keywords
somatic hypermutation; germinal center; Burkitt's lymphoma; c-Myc
Funding
- German Jose Carreras Leukemia Foundation [SP/03/10, R05/10v]
- Wilhelm Sander foundation [2003.046.2]
- Deutsche Forschungsgemeinschaft [TRR54-TPA4]
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The germinal center (GC) reaction has a pivotal function in human B-cell lymphomagenesis. Genetic aberrations occurring during somatic hypermutation and class switch recombination deregulate key factors controlling B-cell physiology and proliferation. Several human lymphoma entities are characterized by a constitutive GC phenotype and ongoing somatic hypermutation, but the molecular basis for this phenomenon is only partly understood. We have investigated the reasons for a constitutive GC-like program in Burkitt's lymphoma cells. Here, overexpression of c-Myc leads to a centroblast phenotype, promotes high constitutive expression of the key GC factors Bcl-6, E2A and activation-induced cytidine deaminase and contributes to proliferation and somatic hypermutation. Our findings elucidate how the activity of a pivotal transcription factor may freeze B-cell lymphoma cells in a constitutive GC-like state that is even maintained at an extrafollicular location. Oncogene (2010) 29, 888-897; doi:10.1038/onc.2009.377; published online 2 November 2009
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