TitleThe epigenetic basis of diffuse large B-cell lymphoma.
Publication TypeJournal Article
Year of Publication2015
AuthorsJiang, Yanwen, and Melnick Ari
JournalSemin Hematol
Volume52
Issue2
Pagination86-96
Date Published2015 Apr
ISSN1532-8686
KeywordsAnimals, B-Lymphocytes, DNA Methylation, Epigenesis, Genetic, Humans, Lymphoma, Large B-Cell, Diffuse, Mutation
Abstract

<p>The pathogenesis of diffuse large B-cell lymphoma (DLBCL) is strongly linked to perturbation of epigenetic mechanisms. The germinal center (GC) B cells from which DLBCLs arise are prone to instability in their cytosine methylation patterns. DLBCLs inherit this epigenetic instability and display variable degrees of epigenetic heterogeneity. Greater epigenetic heterogeneity is linked with poor clinical outcome. Somatic mutations of histone-modifying proteins have also emerged as a hallmark of DLBCL. The effect of these somatic mutations may be to disrupt epigenetic switches that control the GC phenotype and "lock in" certain oncogenic features of GC B cells, resulting in malignant transformation. DNA methyltransferase and histone methyltransferase inhibitors are emerging as viable therapeutic approaches to erase aberrant epigenetic programming, suppress DLBCL growth, and overcome chemotherapy resistance. This review will discuss these recent advances and their therapeutic implications.</p>

DOI10.1053/j.seminhematol.2015.01.003
Alternate JournalSemin Hematol
PubMed ID25805588
PubMed Central IDPMC4374125
Grant ListR01 CA104348 / CA / NCI NIH HHS / United States
R01 CA187109 / CA / NCI NIH HHS / United States
R01CA187109 / CA / NCI NIH HHS / United States