Aberrantly elevated suprabasin in the bone marrow as a candidate biomarker of advanced disease state in myelodysplastic syndromes.
Antigens, Differentiation
/ blood
Azacitidine
/ pharmacology
Biomarkers
/ blood
Bone Marrow
/ metabolism
Cell Compartmentation
/ drug effects
Cell Line, Tumor
Chemokine CCL2
/ metabolism
Gene Expression Regulation, Neoplastic
HEK293 Cells
Humans
Interferon-gamma
/ pharmacology
Leukocytes, Mononuclear
/ metabolism
Lymphocyte Count
Myelodysplastic Syndromes
/ blood
Myeloid Cells
/ drug effects
Neoplasm Proteins
/ blood
Prognosis
Proto-Oncogene Mas
RNA, Messenger
/ genetics
5-azacytidine
MDS
MDSCs
biomarker
suprabasin
Journal
Molecular oncology
ISSN: 1878-0261
Titre abrégé: Mol Oncol
Pays: United States
ID NLM: 101308230
Informations de publication
Date de publication:
10 2020
10 2020
Historique:
received:
06
06
2020
revised:
06
07
2020
accepted:
16
07
2020
pubmed:
23
7
2020
medline:
11
9
2021
entrez:
23
7
2020
Statut:
ppublish
Résumé
Myelodysplastic syndromes (MDS) are preleukemic disorders characterized by clonal growth of mutant hematopoietic stem and progenitor cells. MDS are associated with proinflammatory signaling, dysregulated immune response, and cell death in the bone marrow (BM). Aging, autoinflammation and autoimmunity are crucial features of disease progression, concordant with promoting growth of malignant clones and accumulation of mutations. Suprabasin (SBSN), a recently proposed proto-oncogene of unknown function, physiologically expressed in stratified epithelia, is associated with poor prognosis of several human malignancies. Here, we showed that SBSN is expressed in the BM by myeloid cell subpopulations, including myeloid-derived suppressor cells, and is secreted into BM plasma and peripheral blood of MDS patients. The highest expression of SBSN was present in a patient group with poor prognosis. SBSN levels in the BM correlated positively with blast percentage and negatively with CCL2 chemokine levels and lymphocyte count. In vitro treatment of leukemic cells with interferon-gamma and demethylating agent 5-azacytidine (5-AC) induced SBSN expression. This indicated that aberrant cytokine levels in the BM and epigenetic landscape modifications in MDS patients may underlie ectopic expression of SBSN. Our findings suggest SBSN as a candidate biomarker of high-risk MDS with a possible role in disease progression and therapy resistance.
Identifiants
pubmed: 32696549
doi: 10.1002/1878-0261.12768
pmc: PMC7530796
doi:
Substances chimiques
Antigens, Differentiation
0
Biomarkers
0
Chemokine CCL2
0
MAS1 protein, human
0
Neoplasm Proteins
0
Proto-Oncogene Mas
0
RNA, Messenger
0
SBSN protein, human
0
Interferon-gamma
82115-62-6
Azacitidine
M801H13NRU
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2403-2419Informations de copyright
© 2020 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.
Références
Cancer. 2005 Aug 15;104(4):788-93
pubmed: 15973668
Oncoimmunology. 2015 Jun 24;5(2):e1062208
pubmed: 27057428
Leukemia. 2012 Apr;26(4):693-9
pubmed: 21912394
PLoS One. 2012;7(11):e48582
pubmed: 23144906
Sci Rep. 2016 Feb 22;6:21549
pubmed: 26899563
Eur J Immunol. 2013 Nov;43(11):2930-42
pubmed: 23878002
J Biol Chem. 2002 Nov 22;277(47):45195-202
pubmed: 12228223
J Clin Invest. 2013 Nov;123(11):4595-611
pubmed: 24216507
J Clin Oncol. 2012 Mar 10;30(8):820-9
pubmed: 22331955
Leukemia. 2018 Dec;32(12):2659-2671
pubmed: 29858584
Mol Oncol. 2019 Jul;13(7):1467-1489
pubmed: 30919591
Genomics. 2004 Aug;84(2):384-97
pubmed: 15234001
Pathobiology. 2019;86(1):7-13
pubmed: 30041243
Carcinogenesis. 2020 Nov 13;41(11):1543-1552
pubmed: 32055838
Blood. 2018 Oct 11;132(15):1553-1560
pubmed: 30104218
PLoS One. 2017 Jan 12;12(1):e0170261
pubmed: 28081565
Gene. 2004 Jun 9;334:123-31
pubmed: 15256262
J Clin Oncol. 2020 May 20;38(15):1723-1735
pubmed: 32058844
Leukemia. 2018 Mar;32(3):588-596
pubmed: 28819278
J Immunol. 1997 May 1;158(9):4129-36
pubmed: 9126972
Blood. 2017 Mar 30;129(13):1791-1801
pubmed: 28126925
Cancer Sci. 2014 Dec;105(12):1533-40
pubmed: 25283635
Nat Rev Immunol. 2009 Mar;9(3):162-74
pubmed: 19197294
Blood. 2019 Mar 7;133(10):1039-1048
pubmed: 30670444
Sci Rep. 2019 Sep 2;9(1):12647
pubmed: 31477761
J Exp Med. 2011 Sep 26;208(10):1949-62
pubmed: 21930770
Blood Cancer J. 2019 Aug 9;9(8):63
pubmed: 31399557
Blood. 2013 May 9;121(19):3811-7
pubmed: 23660859
Cancer Immunol Res. 2017 Jan;5(1):3-8
pubmed: 28052991
J Clin Endocrinol Metab. 2015 Feb;100(2):744-53
pubmed: 25393639
J Proteome Res. 2011 Jul 1;10(7):3149-59
pubmed: 21574646
Blood. 2016 May 19;127(20):2391-405
pubmed: 27069254
J Interferon Cytokine Res. 2009 Jun;29(6):313-26
pubmed: 19441883
Nat Med. 2014 Dec;20(12):1472-8
pubmed: 25326804
Leukemia. 2009 Jul;23(7):1288-96
pubmed: 19282834
Leukemia. 2014 Feb;28(2):241-7
pubmed: 24220272
Blood. 2019 Mar 7;133(10):1049-1059
pubmed: 30670442
Medicine (Baltimore). 2019 May;98(22):e15844
pubmed: 31145332
PLoS One. 2012;7(7):e40389
pubmed: 22792300
Blood. 2013 Nov 21;122(22):3616-27; quiz 3699
pubmed: 24030381
Blood. 2009 Jul 30;114(5):937-51
pubmed: 19357394
Cell Death Differ. 2015 Jun;22(6):898-911
pubmed: 25012501
Leuk Res. 2015 Oct;39(10):1020-7
pubmed: 26276090
Blood. 2019 Feb 7;133(6):521-529
pubmed: 30545832
J Dermatol Sci. 2019 Sep;95(3):107-112
pubmed: 31399284
Cell Mol Life Sci. 2013 Oct;70(20):3813-27
pubmed: 23423530
Nat Methods. 2009 May;6(5):343-5
pubmed: 19363495
Blood. 1997 Mar 15;89(6):2079-88
pubmed: 9058730
Blood. 2016 Dec 22;128(25):2960-2975
pubmed: 27737891
Blood. 2000 Jun 1;95(11):3273-9
pubmed: 10828005
Oncoimmunology. 2016 May 13;5(10):e1183860
pubmed: 27853634