Platelet proteo-transcriptomic profiling validates mediators of thrombosis and proteostasis in patients with myeloproliferative neoplasms.
Journal
bioRxiv : the preprint server for biology
Titre abrégé: bioRxiv
Pays: United States
ID NLM: 101680187
Informations de publication
Date de publication:
26 Oct 2023
26 Oct 2023
Historique:
pubmed:
14
11
2023
medline:
14
11
2023
entrez:
14
11
2023
Statut:
epublish
Résumé
Patients with chronic Myeloproliferative Neoplasms (MPN) including polycythemia vera (PV) and essential thrombocythemia (ET) exhibit unique clinical features, such as a tendency toward thrombosis and hemorrhage, and risk of disease progression to secondary bone marrow fibrosis and/or acute leukemia. Although an increase in blood cell lineage counts (quantitative features) contribute to these morbid sequelae, the significant qualitative abnormalities of myeloid cells that contribute to vascular risk are not well understood. Here, we address this critical knowledge gap via a comprehensive and untargeted profiling of the platelet proteome in a large (n= 140) cohort of patients (from two independent sites) with an established diagnosis of PV and ET (and complement prior work on the MPN platelet transcriptome from a third site). We discover distinct MPN platelet protein expression and confirm key molecular impairments associated with proteostasis and thrombosis mechanisms of potential relevance to MPN pathology. Specifically, we validate expression of high-priority candidate markers from the platelet transcriptome at the platelet proteome (
Identifiants
pubmed: 37961700
doi: 10.1101/2023.10.23.563619
pmc: PMC10634751
pii:
doi:
Types de publication
Preprint
Langues
eng
Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : NHGRI NIH HHS
ID : K08 HG010061
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG011762
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001085
Pays : United States
Références
J Cell Mol Med. 2021 Jan;25(2):1024-1034
pubmed: 33277798
Nat Rev Genet. 2018 May;19(5):299-310
pubmed: 29479082
J Alzheimers Dis. 2020;74(4):1097-1106
pubmed: 32144986
Cell Syst. 2015 Dec 23;1(6):417-425
pubmed: 26771021
J Thromb Haemost. 2021 Oct;19(10):2583-2595
pubmed: 34161660
Int J Mol Sci. 2017 Mar 08;18(3):
pubmed: 28282906
Mol Cell. 2020 Jan 2;77(1):138-149.e5
pubmed: 31735643
Blood. 2010 Jan 21;115(3):667-76
pubmed: 19965650
Nat Rev Genet. 2020 Oct;21(10):630-644
pubmed: 32709985
Leuk Lymphoma. 2020 Dec;61(13):3052-3065
pubmed: 32799592
Immun Inflamm Dis. 2021 Mar;9(1):196-209
pubmed: 33277966
Curr Opin Chem Biol. 2023 Apr;73:102253
pubmed: 36689818
Nat Med. 2016 Jan;22(1):20-1
pubmed: 26735404
FEBS J. 2019 Jan;286(2):241-278
pubmed: 30027602
Clin Cancer Res. 2021 Oct 15;27(20):5708-5717
pubmed: 34400417
J Thromb Haemost. 2015 Jun;13(6):893-908
pubmed: 25900780
Int J Mol Sci. 2022 Jul 11;23(14):
pubmed: 35886993
Blood. 2014 Dec 18;124(26):3967-77
pubmed: 25298036
Proteomics Clin Appl. 2016 Aug;10(8):767-73
pubmed: 26948058
PLoS One. 2015 Aug 14;10(8):e0135463
pubmed: 26275051
Adv Mater. 2018 Dec;30(52):e1805308
pubmed: 30368954
Cell. 2009 Apr 17;137(2):332-43
pubmed: 19379698
Am J Hematol. 2019 Jan;94(1):133-143
pubmed: 30281843
Br J Cancer. 2022 Feb;126(3):316-322
pubmed: 34811507
J Biol Chem. 2019 Apr 5;294(14):5246-5260
pubmed: 30737284
Apoptosis. 2013 May;18(5):566-77
pubmed: 23456624
J Thromb Haemost. 2023 Jun;21(6):1397-1408
pubmed: 36931602
Proteomes. 2019 May 06;7(2):
pubmed: 31064135
Blood. 2013 Jan 17;121(3):431-9
pubmed: 23086754
Leukemia. 2022 Jul;36(7):1703-1719
pubmed: 35732831
Blood. 2013 Feb 14;121(7):1209-19
pubmed: 23243278
Int J Mol Sci. 2023 May 14;24(10):
pubmed: 37240094
J Clin Oncol. 2023 Jul 1;41(19):3534-3544
pubmed: 37126762
Cold Spring Harb Perspect Med. 2020 Feb 3;10(2):
pubmed: 31548225
Cells. 2022 Sep 06;11(18):
pubmed: 36139353
Nat Commun. 2020 Jul 13;11(1):3479
pubmed: 32661250
Front Cell Dev Biol. 2021 Mar 29;9:641836
pubmed: 33855021
Curr Opin Hematol. 2023 Sep 1;30(5):167-174
pubmed: 37459354
J Biol Chem. 2000 Oct 27;275(43):33844-9
pubmed: 10938270
Blood Adv. 2023 May 9;7(9):1650-1665
pubmed: 36508284
Mol Syst Biol. 2017 Sep 26;13(9):942
pubmed: 28951502
Genome Biol. 2014;15(12):550
pubmed: 25516281
Science. 2020 Apr 24;368(6489):
pubmed: 32327570
Clin Cancer Res. 2000 Dec;6(12):4823-30
pubmed: 11156241
Blood Cancer Discov. 2022 Jul 6;3(4):298-315
pubmed: 35405004
J Thromb Haemost. 2014 Oct;12(10):1580-90
pubmed: 25302663
Curr Opin Hematol. 2013 Jul;20(4):327-35
pubmed: 23695449
Am J Hematol. 2023 May;98(5):801-821
pubmed: 36680511
Am J Hematol. 1998 Apr;57(4):277-82
pubmed: 9544970
Cell Oncol (Dordr). 2018 Oct;41(5):541-553
pubmed: 29946821
Ann Intern Med. 2018 Mar 6;168(5):317-325
pubmed: 29335713
Cell Biochem Funct. 2020 Jun;38(4):362-372
pubmed: 31885098
Hematology Am Soc Hematol Educ Program. 2022 Dec 9;2022(1):225-234
pubmed: 36485130
Virchows Arch. 2023 Jan;482(1):53-68
pubmed: 36580136
Blood. 2021 Mar 4;137(9):1145-1153
pubmed: 33237986
J Clin Oncol. 2018 Jun 10;36(17):1769-1770
pubmed: 29708808
Proteomics. 2018 Aug;18(15):e1800219
pubmed: 29932309
Sci Rep. 2023 Aug 31;13(1):14253
pubmed: 37653079
Blood Rev. 2020 Jul;42:100711
pubmed: 32505517
Platelets. 2023 Dec;34(1):2224454
pubmed: 37313659
Blood Adv. 2021 Jan 12;5(1):113-121
pubmed: 33570633
Oxid Med Cell Longev. 2017;2017:3017947
pubmed: 28546851
Br J Haematol. 2021 Nov;195(3):338-351
pubmed: 34409596
Exp Hematol. 2014 May;42(5):360-8
pubmed: 24463275
Blood Cancer J. 2019 Aug 8;9(8):61
pubmed: 31395856
J Hematol Oncol. 2015 Jun 18;8:71
pubmed: 26081257
J Thromb Haemost. 2023 Aug;21(8):2137-2150
pubmed: 37037379
Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50
pubmed: 16199517
Blood. 2016 May 19;127(20):2391-405
pubmed: 27069254
Blood Adv. 2019 Aug 13;3(15):2368-2380
pubmed: 31399401
Science. 2023 Apr 14;380(6641):178-187
pubmed: 37053338
Proteomics Clin Appl. 2019 May;13(3):e1800162
pubmed: 30318839
J Proteome Res. 2009 Jun;8(6):2903-14
pubmed: 19341245
Cell. 2005 Feb 11;120(3):303-13
pubmed: 15707890
Nat Med. 2016 Jan;22(1):91-6
pubmed: 26692333
Blood. 2020 Apr 9;135(15):1255-1269
pubmed: 32068780
Cells. 2021 Dec 16;10(12):
pubmed: 34944059
Curr Genomics. 2013 Apr;14(2):91-110
pubmed: 24082820
Exp Cell Res. 2019 Sep 15;382(2):111472
pubmed: 31229505
Arterioscler Thromb Vasc Biol. 2015 Dec;35(12):2554-61
pubmed: 26471268
Oncotarget. 2015 Nov 17;6(36):39262-75
pubmed: 26513020
Am J Physiol Cell Physiol. 2022 Oct 1;323(4):C951-C958
pubmed: 35993516
Nat Rev Cancer. 2010 Aug;10(8):537-49
pubmed: 20651736
Haematologica. 2006 Feb;91(2):169-75
pubmed: 16461300
Arterioscler Thromb Vasc Biol. 2021 Mar;41(3):999-1011
pubmed: 33441027
Front Immunol. 2018 Jun 11;9:1298
pubmed: 29942307
Blood Adv. 2018 Sep 11;2(17):2187-2198
pubmed: 30185436
Nucleic Acids Res. 2022 Jan 7;50(D1):D543-D552
pubmed: 34723319
Leukemia. 2019 Mar;33(3):671-685
pubmed: 30206308
Leuk Lymphoma. 2021 Nov;62(11):2703-2715
pubmed: 34098836
Cell Rep Med. 2021 Oct 19;2(10):100425
pubmed: 34755136
Am J Hum Genet. 2015 Apr 2;96(4):532-42
pubmed: 25772935
J Cell Mol Med. 2013 Nov;17(11):1385-96
pubmed: 24237791
Exp Hematol. 2021 Dec;104:48-54
pubmed: 34601067
Leukemia. 2023 Feb;37(2):359-369
pubmed: 36473980
Hematology Am Soc Hematol Educ Program. 2012;2012:571-81
pubmed: 23233637
Cells. 2020 Mar 02;9(3):
pubmed: 32121660
Biomolecules. 2022 Nov 26;12(12):
pubmed: 36551184
J Thromb Haemost. 2018 May;16(5):946-959
pubmed: 29512284
Blood. 2015 Jul 30;126(5):582-8
pubmed: 26109205
Blood. 2011 Sep 1;118(9):2599-601
pubmed: 21750318