c-Myc overexpression promotes a germinal center-like program in Burkitt's lymphoma.
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.
Scheller
H
H
Institute of Clinical Molecular Biology, Helmholtz Center Munich, German Research Center for Environmental Health, Munich, Germany.
Tobollik
S
S
Kutzera
A
A
Eder
M
M
Unterlehberg
J
J
Pfeil
I
I
Jungnickel
B
B
D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D002051:Burkitt Lymphoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D003564:Cytidine Deaminase / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D018858:Germinal Center / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D010641:Phenotype; D051560:Proto-Oncogene Proteins c-bcl-6; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D027041:Somatic Hypermutation, Immunoglobulin; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
D051792:Basic Helix-Loop-Helix Proteins; D003564:Cytidine Deaminase; D004268:DNA-Binding Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; D016271:Proto-Oncogene Proteins c-myc; D000098830:AICDA (Activation-Induced Cytidine Deaminase); C084103:BCL6 protein, human; C407909:TCF3 protein, human