title: The epigenetic basis of diffuse large B-cell lymphoma.
abstract: 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.
authors: Institute for Computational Biomedicine, Weill Cornell Medical College, New York, NY, USA; Department of Medicine, Weill Cornell Medical College, New York, NY, USA; Sandra and Edward Meyer Cancer Center, Weill Cornell Medical College, New York, NY, USA.
authors: Yanwen
authors: Y
authors: Jiang
authors: Department of Medicine, Weill Cornell Medical College, New York, NY, USA; Sandra and Edward Meyer Cancer Center, Weill Cornell Medical College, New York, NY, USA. Electronic address: amm2014@med.cornell.edu.
authors: Ari
authors: A
authors: Melnick
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics*; D009154:Mutation