All-trans retinoic acid enhances, and a pan-RAR antagonist counteracts, the stem cell promoting activity of EVI1 in acute myeloid leukemia.
Animals
Apoptosis
/ drug effects
Carcinogenesis
/ drug effects
Cell Proliferation
/ drug effects
Disease Models, Animal
Gene Expression Regulation, Leukemic
/ drug effects
Humans
Leukemia, Myeloid, Acute
/ genetics
MDS1 and EVI1 Complex Locus Protein
/ genetics
Mice
Myeloid Cells
/ drug effects
Neoplastic Stem Cells
/ metabolism
Receptor, Notch4
/ genetics
Tretinoin
/ metabolism
Journal
Cell death & disease
ISSN: 2041-4889
Titre abrégé: Cell Death Dis
Pays: England
ID NLM: 101524092
Informations de publication
Date de publication:
10 12 2019
10 12 2019
Historique:
received:
06
09
2019
accepted:
21
11
2019
revised:
20
11
2019
entrez:
12
12
2019
pubmed:
12
12
2019
medline:
12
9
2020
Statut:
epublish
Résumé
Ecotropic virus integration site 1 (EVI1), whose overexpression characterizes a particularly aggressive subtype of acute myeloid leukemia (AML), enhanced anti-leukemic activities of all-trans retinoic acid (atRA) in cell lines and patient samples. However, the drivers of leukemia formation, therapy resistance, and relapse are leukemic stem cells (LSCs), whose properties were hardly reflected in these experimental setups. The present study was designed to address the effects of, and interactions between, EVI1 and retinoids in AML LSCs. We report that Evi1 reduced the maturation of leukemic cells and promoted the abundance, quiescence, and activity of LSCs in an MLL-AF9-driven mouse model of AML. atRA further augmented these effects in an Evi1 dependent manner. EVI1 also strongly enhanced atRA regulated gene transcription in LSC enriched cells. One of their jointly regulated targets, Notch4, was an important mediator of their effects on leukemic stemness. In vitro exposure of leukemic cells to a pan-RAR antagonist caused effects opposite to those of atRA. In vivo antagonist treatment delayed leukemogenesis and reduced LSC abundance, quiescence, and activity in Evi1
Identifiants
pubmed: 31822659
doi: 10.1038/s41419-019-2172-2
pii: 10.1038/s41419-019-2172-2
pmc: PMC6904467
doi:
Substances chimiques
MDS1 and EVI1 Complex Locus Protein
0
MECOM protein, human
0
Mecom protein, mouse
0
Receptor, Notch4
0
Notch4 protein, mouse
146991-60-8
Tretinoin
5688UTC01R
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
944Subventions
Organisme : Austrian Science Fund FWF
ID : P 27132
Pays : Austria
Organisme : Austrian Science Fund FWF
ID : P 28256
Pays : Austria
Organisme : Austrian Science Fund (Fonds zur Förderung der Wissenschaftlichen Forschung)
ID : P28256-B28
Pays : International
Références
J Exp Med. 2006 May 15;203(5):1283-93
pubmed: 16682494
Leukemia. 2013 Jun;27(6):1369-80
pubmed: 23228968
Gene. 2007 Jul 15;396(2):346-57
pubmed: 17507183
Mech Dev. 1997 Jul;65(1-2):55-70
pubmed: 9256345
J Clin Oncol. 2013 Jan 1;31(1):95-103
pubmed: 23008312
J Exp Med. 2011 Nov 21;208(12):2403-16
pubmed: 22084405
Blood. 2012 Jun 14;119(24):5838-49
pubmed: 22553314
Cancer Res. 2007 Jun 15;67(12):5658-66
pubmed: 17575132
Oncotarget. 2018 Apr 6;9(26):18341-18350
pubmed: 29719609
Gene. 2004 Mar 17;328:1-16
pubmed: 15019979
Blood. 2016 Jan 7;127(1):29-41
pubmed: 26660431
J Immunol Methods. 2009 Aug 15;347(1-2):70-8
pubmed: 19567251
Oncol Lett. 2016 Nov;12(5):3499-3505
pubmed: 27900027
FEBS J. 2009 Nov;276(22):6810-22
pubmed: 19843176
Am J Respir Cell Mol Biol. 2005 Dec;33(6):622-8
pubmed: 16141447
Cell. 2017 May 18;169(5):807-823.e19
pubmed: 28479188
Cancer Cell. 2016 Jul 11;30(1):43-58
pubmed: 27344946
Ann Hematol. 2016 Dec;95(12):1931-1942
pubmed: 27696203
Leukemia. 2004 Apr;18(4):777-87
pubmed: 14961038
Oncogene. 1998 Apr 30;16(17):2287-91
pubmed: 9619838
Blood. 2016 Jan 28;127(4):458-63
pubmed: 26582376
Anticancer Res. 2014 Jan;34(1):69-80
pubmed: 24403446
Nat Med. 2010 Feb;16(2):198-204
pubmed: 20098431
Cancer Cell. 2014 Apr 14;25(4):415-27
pubmed: 24703906
Blood. 2011 Jun 9;117(23):6304-14
pubmed: 21190993
Cell Death Dis. 2017 May 11;8(5):e2782
pubmed: 28492552
Blood. 2011 Oct 6;118(14):3853-61
pubmed: 21666053
Cancer Lett. 2005 Feb 28;219(1):27-31
pubmed: 15694661
Blood. 2013 Oct 17;122(16):2888-92
pubmed: 24021671
Hepatobiliary Pancreat Dis Int. 2013 Jun;12(3):286-94
pubmed: 23742774
Sci Rep. 2019 Jun 24;9(1):9139
pubmed: 31235852
Genes Chromosomes Cancer. 2008 Apr;47(4):288-98
pubmed: 18181178
Blood. 2016 Jun 9;127(23):2867-78
pubmed: 27103744
Cell Rep. 2013 Dec 26;5(6):1704-13
pubmed: 24332856
Cochrane Database Syst Rev. 2018 Aug 06;8:CD011960
pubmed: 30080246
Blood. 2008 Apr 15;111(8):4329-37
pubmed: 18272813
Cancer Sci. 2016 Aug;107(8):1079-91
pubmed: 27234159
EMBO J. 2005 Jun 1;24(11):1976-87
pubmed: 15889140
Blood. 2000 Jan 15;95(2):470-7
pubmed: 10627451
Blood. 1999 Jul 15;94(2):483-95
pubmed: 10397716
Cell Cycle. 2014;13(18):2931-43
pubmed: 25486480
PLoS One. 2013 Jun 27;8(6):e67134
pubmed: 23826213
Oncotarget. 2017 Jun 6;8(23):37041-37060
pubmed: 27419624
N Engl J Med. 2016 Jun 9;374(23):2209-2221
pubmed: 27276561
Leukemia. 2013 Apr;27(4):852-60
pubmed: 23235717
Nat Commun. 2018 Oct 12;9(1):4239
pubmed: 30315161
Proc Natl Acad Sci U S A. 2013 Nov 19;110(47):18820-5
pubmed: 24191050
Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50
pubmed: 16199517
Stem Cell Investig. 2015 Apr 29;2:8
pubmed: 27358876
Blood. 2013 May 16;121(20):4142-55
pubmed: 23547050
Cell Stem Cell. 2008 Aug 7;3(2):207-20
pubmed: 18682242
Nature. 2006 Aug 17;442(7104):818-22
pubmed: 16862118
J Cancer. 2018 Jun 12;9(13):2374-2379
pubmed: 30026833
Cell. 2014 Apr 10;157(2):369-381
pubmed: 24703711
Leukemia. 2004 Nov;18(11):1798-803
pubmed: 15385923
Proc Natl Acad Sci U S A. 2012 Feb 7;109(6):2168-73
pubmed: 22308434
J Clin Oncol. 2010 Apr 20;28(12):2101-7
pubmed: 20308656
Blood. 2010 Feb 4;115(5):948-56
pubmed: 19965647
Oncogene. 2014 Oct 16;33(42):5028-38
pubmed: 24747972
Nature. 1998 Jul 2;394(6688):92-6
pubmed: 9665135
Endocrinology. 2016 Apr;157(4):1601-12
pubmed: 26812157
Nat Commun. 2016 Jul 11;7:12166
pubmed: 27397025
Contemp Oncol (Pozn). 2015;19(1A):A1-6
pubmed: 25691816
Leukemia. 1997 Mar;11(3):352-8
pubmed: 9067573
EMBO J. 2016 Nov 2;35(21):2315-2331
pubmed: 27638855
Oncol Lett. 2018 Jun;15(6):8749-8755
pubmed: 29805613
Eur J Endocrinol. 1995 Sep;133(3):335-41
pubmed: 7581951