title: Follicular lymphoma, a B cell malignancy addicted to epigenetic mutations.
abstract: While follicular lymphoma (FL) is exquisitely responsive to immuno-chemotherapy, many patients follow a relapsing remitting clinical course driven in part by a common precursor cell (CPC) population. Advances in next generation sequencing have provided valuable insights into the genetic landscape of FL and its clonal evolution in response to therapy, implicating perturbations of epigenetic regulators as a hallmark of the disease. Recurrent mutations of histone modifiers KMT2D, CREBBP, EP300, EZH2, ARIDIA, and linker histones are likely early events arising in the CPC pool, rendering epigenetic based therapies conceptually attractive for treatment of indolent and transformed FL. This review provides a synopsis of the main epigenetic aberrations and the current efforts in development and testing of epigenetic therapies in this B cell malignancy.
authors.affiliation: a Centre for Haemato-Oncology, Barts Cancer Institute , Queen Mary University of London , London , United Kingdom.
authors.forename: Koorosh
authors.initials: K
authors.lastname: Korfi
authors.affiliation: a Centre for Haemato-Oncology, Barts Cancer Institute , Queen Mary University of London , London , United Kingdom.
authors.forename: Sara
authors.initials: S
authors.lastname: Ali
authors.affiliation: a Centre for Haemato-Oncology, Barts Cancer Institute , Queen Mary University of London , London , United Kingdom.
authors.forename: James A
authors.initials: JA
authors.lastname: Heward
authors.affiliation: a Centre for Haemato-Oncology, Barts Cancer Institute , Queen Mary University of London , London , United Kingdom.
authors.forename: Jude
authors.initials: J
authors.lastname: Fitzgibbon
mesh_terms: D001402:B-Lymphocytes / Q000473:pathology; D050882:CREB-Binding Protein / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D050881:E1A-Associated p300 Protein / Q000235:genetics; D000071221:Enhancer of Zeste Homolog 2 Protein / Q000235:genetics; D044127:Epigenesis, Genetic; D059014:High-Throughput Nucleotide Sequencing; D006657:Histones / Q000235:genetics; D006801:Humans; D008224:Lymphoma, Follicular / Q000235:genetics* / Q000473:pathology; D009154:Mutation / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000473:pathology
chemical_list: D004268:DNA-Binding Proteins; D006657:Histones; C120898:KMT2D protein, human; D009363:Neoplasm Proteins; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D050882:CREB-Binding Protein; C494363:CREBBP protein, human; D050881:E1A-Associated p300 Protein; C494360:EP300 protein, human
keywords: EZH2 inhibitors; Epigenetic mutations; HDAC inhibitors; epigenetic therapies; follicular lymphoma