Establishment of the lymphoid ETS-code reveals deregulated ETS genes in Hodgkin lymphoma.
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2023
2023
Historique:
received:
05
04
2023
accepted:
16
06
2023
medline:
12
7
2023
pubmed:
10
7
2023
entrez:
10
7
2023
Statut:
epublish
Résumé
The human family of ETS transcription factors numbers 28 genes which control multiple aspects of development, notably the differentiation of blood and immune cells. Otherwise, aberrant expression of ETS genes is reportedly involved in forming leukemia and lymphoma. Here, we comprehensively mapped ETS gene activities in early hematopoiesis, lymphopoiesis and all mature types of lymphocytes using public datasets. We have termed the generated gene expression pattern lymphoid ETS-code. This code enabled identification of deregulated ETS genes in patients with lymphoid malignancies, revealing 12 aberrantly expressed members in Hodgkin lymphoma (HL). For one of these, ETS gene ETV3, expression in stem and progenitor cells in addition to that in developing and mature T-cells was mapped together with downregulation in B-cell differentiation. In contrast, subsets of HL patients aberrantly overexpressed ETV3, indicating oncogenic activity in this B-cell malignancy. Analysis of ETV3-overexpressing HL cell line SUP-HD1 demonstrated genomic duplication of the ETV3 locus at 1q23, GATA3 as mutual activator, and suppressed BMP-signalling as mutual downstream effect. Additional examination of the neighboring ETS genes ETS1 and FLI1 revealed physiological activities in B-cell development and aberrant downregulation in HL patient subsets. SUP-HD1 showed genomic loss on chromosome 11, del(11)(q22q25), targeting both ETS1 and FLI1, underlying their downregulation. Furthermore, in the same cell line we identified PBX1-mediated overexpression of RIOK2 which inhibited ETS1 and activated JAK2 expression. Collectively, we codified normal ETS gene activities in lymphopoiesis and identified oncogenic ETS members in HL.
Identifiants
pubmed: 37428779
doi: 10.1371/journal.pone.0288031
pii: PONE-D-23-10256
pmc: PMC10332584
doi:
Substances chimiques
Transcription Factors
0
Proto-Oncogene Proteins c-ets
0
Proto-Oncogene Protein c-ets-1
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0288031Informations de copyright
Copyright: © 2023 Nagel et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
Références
Leukemia. 2022 Jul;36(7):1720-1748
pubmed: 35732829
Int J Mol Sci. 2022 Mar 16;23(6):
pubmed: 35328612
Nat Rev Mol Cell Biol. 2001 Nov;2(11):827-37
pubmed: 11715049
Biochem Soc Trans. 2014 Feb;42(1):130-8
pubmed: 24450640
EMBO J. 1996 Jan 2;15(1):125-34
pubmed: 8598195
EMBO J. 2002 Aug 1;21(15):4104-13
pubmed: 12145210
J Allergy Clin Immunol. 2019 Jun;143(6):2321-2325
pubmed: 30825467
Cell. 2018 Oct 4;175(2):598-599
pubmed: 30290144
Blood. 2012 Oct 25;120(17):3530-40
pubmed: 22955918
Nature. 1983 Nov 24-30;306(5941):395-7
pubmed: 6316156
Mol Biol Rep. 2022 Apr;49(4):2915-2924
pubmed: 35064409
Haematologica. 2012 Oct;97(10):1612-4
pubmed: 22581005
Leukemia. 2013 Mar;27(3):671-9
pubmed: 23174882
Am J Dermatopathol. 2022 Jul 1;44(7):529-531
pubmed: 35234186
Blood. 2000 Dec 1;96(12):3681-95
pubmed: 11090048
J Biol Chem. 2010 Dec 31;285(53):41328-36
pubmed: 21036908
Nature. 1995 Oct 19;377(6550):635-8
pubmed: 7566176
Annu Rev Biochem. 2011;80:437-71
pubmed: 21548782
Cell. 2002 Apr 19;109(2):169-80
pubmed: 12007404
J Clin Oncol. 2015 Apr 20;33(12):1379-88
pubmed: 25800755
Cell. 2017 Mar 9;168(6):1086-1100.e10
pubmed: 28283063
Hematol Oncol. 2005 Sep-Dec;23(3-4):127-32
pubmed: 16342298
Cancers (Basel). 2021 Apr 19;13(8):
pubmed: 33921702
EMBO J. 2010 Jul 7;29(13):2147-60
pubmed: 20517297
Cell Stem Cell. 2010 Oct 8;7(4):532-44
pubmed: 20887958
Blood. 1998 Aug 15;92(4):1308-16
pubmed: 9694719
F1000Res. 2022 Apr 13;11:420
pubmed: 35949917
J Immunol. 2008 Aug 1;181(3):1644-54
pubmed: 18641300
Curr Med Chem. 2008;15(4):339-59
pubmed: 18288989
Haematologica. 2011 Jun;96(6):863-70
pubmed: 21393330
Blood. 2013 Sep 26;122(13):2233-41
pubmed: 23926301
Leukemia. 2000 Oct;14(10):1803-14
pubmed: 11021756
EMBO J. 2020 Dec 15;39(24):e104983
pubmed: 33103827
PLoS One. 2021 Nov 22;16(11):e0259674
pubmed: 34807923
Science. 2015 Jun 26;348(6242):aaa5838
pubmed: 26113727
Genes Chromosomes Cancer. 2013 Aug;52(8):741-7
pubmed: 23630094
Immunology. 2011 Nov;134(3):349-59
pubmed: 21978004
PLoS One. 2020 Apr 23;15(4):e0231639
pubmed: 32324763
Sci Rep. 2019 Jun 3;9(1):8218
pubmed: 31160637
Leukemia. 1994 Jan;8(1):72-80
pubmed: 8289502
J Clin Invest. 2003 Feb;111(4):529-37
pubmed: 12588891
Int J Mol Sci. 2021 Oct 22;22(21):
pubmed: 34768865
Blood Cells Mol Dis. 2013 Dec;51(4):248-55
pubmed: 23927967
J Biol Chem. 2008 Jan 11;283(2):951-62
pubmed: 17977828
Nat Immunol. 2023 Jan;24(1):84-95
pubmed: 36543959
Blood. 2015 Nov 12;126(20):2344-5
pubmed: 26438513
PLoS One. 2012;7(10):e46117
pubmed: 23049692
Breast Cancer Res Treat. 2013 Feb;138(1):37-45
pubmed: 23329352
Annu Rev Immunol. 2014;32:283-321
pubmed: 24471430
Blood. 2008 Jan 1;111(1):292-301
pubmed: 17720884
Nat Immunol. 2015 Dec;16(12):1282-91
pubmed: 26502406
Mol Cell Biol. 1999 Mar;19(3):2231-41
pubmed: 10022910
PLoS One. 2021 Feb 4;16(2):e0246603
pubmed: 33539429
J Pathol. 2005 Oct;207(2):243-9
pubmed: 16041695
J Immunol. 2009 Jul 15;183(2):1179-87
pubmed: 19553523
Nat Immunol. 2022 Jan;23(1):109-121
pubmed: 34937919
Nucleic Acids Res. 2003 Oct 1;31(19):5483-9
pubmed: 14500810
Cancer Res. 2005 Sep 1;65(17):7628-34
pubmed: 16140928
Bioessays. 2002 Apr;24(4):362-70
pubmed: 11948622
J Exp Med. 2008 Sep 29;205(10):2251-68
pubmed: 18794340
Cell Rep. 2019 Feb 5;26(6):1627-1640.e7
pubmed: 30726743
Virchows Arch. 2019 Aug;475(2):163-174
pubmed: 30953147
Eur J Cancer. 2005 Nov;41(16):2462-78
pubmed: 16213704
FEMS Microbiol Rev. 2005 Apr;29(2):231-62
pubmed: 15808743
Genome Biol. 2007;8(9):R183
pubmed: 17784955
Leukemia. 2021 Apr;35(4):968-981
pubmed: 33686198
Leuk Lymphoma. 2015 Feb;56(2):480-91
pubmed: 24844359
J Exp Clin Cancer Res. 2021 Nov 11;40(1):357
pubmed: 34763718
Mol Cell. 2001 Dec;8(6):1267-76
pubmed: 11779502
Leukemia. 2011 Sep;25(9):1379-88
pubmed: 21566654
Oncogene. 2000 Dec 18;19(55):6432-42
pubmed: 11175359