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A B Cell Regulome Links Notch to Downstream Oncogenic Pathways in Small B Cell Lymphomas.
Ryan, Russell J H; Petrovic, Jelena; Rausch, Dylan M; Zhou, Yeqiao; Lareau, Caleb A; Kluk, Michael J; Christie, Amanda L; Lee, Winston Y; Tarjan, Daniel R; Guo, Bingqian; Donohue, Laura K H; Gillespie, Shawn M; Nardi, Valentina; Hochberg, Ephraim P; Blacklow, Stephen C; Weinstock, David M; Faryabi, Robert B; Bernstein, Bradley E; Aster, Jon C; Pear, Warren S.
Afiliação
  • Ryan RJH; Department of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA; Broad Institute of MIT and Harvard University, Cambridge, MA 02142, USA.
  • Petrovic J; Department of Pathology and Laboratory Medicine, Abramson Family Cancer Research Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Rausch DM; Department of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA; Broad Institute of MIT and Harvard University, Cambridge, MA 02142, USA.
  • Zhou Y; Department of Pathology and Laboratory Medicine, Abramson Family Cancer Research Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Lareau CA; Department of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA; Broad Institute of MIT and Harvard University, Cambridge, MA 02142, USA.
  • Kluk MJ; Department of Pathology, Weill Cornell School of Medicine, New York, NY 10065, USA.
  • Christie AL; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
  • Lee WY; Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA.
  • Tarjan DR; Department of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA; Broad Institute of MIT and Harvard University, Cambridge, MA 02142, USA.
  • Guo B; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
  • Donohue LKH; Department of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA; Broad Institute of MIT and Harvard University, Cambridge, MA 02142, USA.
  • Gillespie SM; Department of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA; Broad Institute of MIT and Harvard University, Cambridge, MA 02142, USA.
  • Nardi V; Department of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Hochberg EP; Department of Medicine, MGH Cancer Center, Massachusetts General Hospital, Boston, MA 02140, USA.
  • Blacklow SC; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
  • Weinstock DM; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
  • Faryabi RB; Department of Pathology and Laboratory Medicine, Abramson Family Cancer Research Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Bernstein BE; Department of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA; Broad Institute of MIT and Harvard University, Cambridge, MA 02142, USA. Electronic address: bernstein.bradley@mgh.harvard.edu.
  • Aster JC; Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA. Electronic address: jaster@rics.bwh.harvard.edu.
  • Pear WS; Department of Pathology and Laboratory Medicine, Abramson Family Cancer Research Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: wpear@mail.med.upenn.edu.
Cell Rep ; 21(3): 784-797, 2017 Oct 17.
Article em En | MEDLINE | ID: mdl-29045844
ABSTRACT
Gain-of-function Notch mutations are recurrent in mature small B cell lymphomas such as mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL), but the Notch target genes that contribute to B cell oncogenesis are largely unknown. We performed integrative analysis of Notch-regulated transcripts, genomic binding of Notch transcription complexes, and genome conformation data to identify direct Notch target genes in MCL cell lines. This B cell Notch regulome is largely controlled through Notch-bound distal enhancers and includes genes involved in B cell receptor and cytokine signaling and the oncogene MYC, which sustains proliferation of Notch-dependent MCL cell lines via a Notch-regulated lineage-restricted enhancer complex. Expression of direct Notch target genes is associated with Notch activity in an MCL xenograft model and in CLL lymph node biopsies. Our findings provide key insights into the role of Notch in MCL and other B cell malignancies and have important implications for therapeutic targeting of Notch-dependent oncogenic pathways.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Oncogenes / Linfócitos B / Transdução de Sinais / Regulação Neoplásica da Expressão Gênica / Linfoma de Células B / Receptores Notch Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2017 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Oncogenes / Linfócitos B / Transdução de Sinais / Regulação Neoplásica da Expressão Gênica / Linfoma de Células B / Receptores Notch Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2017 Tipo de documento: Article