Role of ETS1 in the Transcriptional Network of Diffuse Large B Cell Lymphoma of the Activated B Cell-Like Type

Cancers
Valdemar PriebeFrancesco Bertoni

Abstract

Diffuse large B cell lymphoma (DLBCL) is a heterogenous disease that has been distinguished into at least two major molecular entities, the germinal center-like B cell (GCB) DLBCL and activated-like B cell (ABC) DLBCL, based on transcriptome expression profiling. A recurrent ch11q24.3 gain is observed in roughly a fourth of DLBCL cases resulting in the overexpression of two ETS transcription factor family members, ETS1 and FLI1. Here, we knocked down ETS1 expression by siRNA and analyzed expression changes integrating them with ChIP-seq data to identify genes directly regulated by ETS1. ETS1 silencing affected expression of genes involved in B cell signaling activation, B cell differentiation, cell cycle, and immune processes. Integration of RNA-Seq (RNA sequencing) data and ChIP-Seq (chromatin immunoprecipitation sequencing) identified 97 genes as bona fide, positively regulated direct targets of ETS1 in ABC-DLBCL. Among these was the Fc receptor for IgM, FCMR (also known as FAIM3 or Toso), which showed higher expression in ABC- than GCB-DLBCL clinical specimens. These findings show that ETS1 is contributing to the lymphomagenesis in a subset of DLBCL and identifies FCMR as a novel target of ETS1, predominantly expressed in AB...Continue Reading

References

Jan 10, 2002·Molecular Cell·C W GarvieC Wolberger
Dec 27, 2005·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Yuka KannoKeiko Ozato
Jun 9, 2006·The New England Journal of Medicine·Michael HummelUNKNOWN Molecular Mechanisms in Malignant Lymphomas Network Project of the Deutsche Krebshilfe
Dec 22, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Alina I MarusinaJohn E Coligan
Jan 23, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Clare PridansStephen L Nutt
Nov 29, 2008·The New England Journal of Medicine·G LenzUNKNOWN Lymphoma/Leukemia Molecular Profiling Project
Jan 6, 2009·Immunological Reviews·Lewis L Lanier
Feb 25, 2009·Nucleic Acids Research·J M RuijterA F M Moorman
Jun 26, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jannek HauserThomas Grundström
Jul 21, 2009·Journal of Molecular Biology·Daniel FitzsimmonsJames Hagman
Oct 28, 2009·The Journal of Experimental Medicine·Hiromi KubagawaJi-Yang Wang
Jan 1, 2010·International Immunology·Hideaki ShimaHiroshi Ohno
Aug 2, 2011·Nature Genetics·Laura PasqualucciRiccardo Dalla-Favera
Sep 13, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Bérengère VireAdrian Wiestner
Dec 26, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Seung-Chul ChoiJohn E Coligan
Jan 5, 2013·Cellular and Molecular Life Sciences : CMLS·Lee Ann Garrett-Sinha
Jun 15, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Wei LuoLee Ann Garrett-Sinha
Oct 9, 2014·Nucleic Acids Research·Joshua P PlotnikPeter C Hollenhorst
Nov 5, 2014·Leukemia & Lymphoma·Monica TestoniFrancesco Bertoni
Mar 4, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Rika OuchidaJi-Yang Wang
Jul 26, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jessica MayeuxAnne B Satterthwaite
Sep 12, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Lisa RussellLee Ann Garrett-Sinha
Sep 24, 2015·Seminars in Cancer Biology·Jürgen Dittmer
Oct 21, 2015·Proceedings of the National Academy of Sciences of the United States of America·Ryan M YoungLouis M Staudt
Dec 2, 2015·Immunity·David Dominguez-SolaRiccardo Dalla-Favera
Jan 8, 2017·The Journal of Pharmacology and Experimental Therapeutics·William G RobichauxJoe B Blumer
Jan 31, 2017·Nature Immunology·Trang T T NguyenNicole Baumgarth
Oct 27, 2017·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Chiara TarantelliFrancesco Bertoni
Apr 19, 2018·Blood·Laura Pasqualucci, Riccardo Dalla-Favera

❮ Previous
Next ❯

Citations

Jun 3, 2021·Cancers·Marta Cuenca, Victor Peperzak

❮ Previous
Next ❯

Datasets Mentioned

BETA
GSE10846
GSE31312

Methods Mentioned

BETA
ChIP-Seq
flow cytometry
FCMR
transfection
electrophoresis
RNA-Seq
transgenic

Software Mentioned

Primer3Plus
FACSDiva
LinRegPCR
FlowJo
R Studio
survminer
GSEA ( Gene Set Enrichment Analysis )
Bioconductor
GSEA
R survival

Related Concepts

Related Feeds

B cell Differentiation

Depending on the signal received through the B cell receptor and other receptors, B cells differentiate into follicular or marginal zone B cells. Here is the latest research pertaining to this differentiation process.

B-Cell Lymphoma

B-cell lymphomas include lymphomas that affect B cells. This subtype of cancer accounts for over 80% of non-Hodgkin lymphomas in the US. Here is the latest research.