Ibrutinib Has Time-dependent On- and Off-target Effects on Plasma Biomarkers and Immune Cells in Chronic Lymphocytic Leukemia.
Journal
HemaSphere
ISSN: 2572-9241
Titre abrégé: Hemasphere
Pays: United States
ID NLM: 101740619
Informations de publication
Date de publication:
May 2021
May 2021
Historique:
received:
10
11
2020
accepted:
22
03
2021
entrez:
29
4
2021
pubmed:
30
4
2021
medline:
30
4
2021
Statut:
epublish
Résumé
Ibrutinib is a covalently binding inhibitor of the B-cell receptor signaling-mediator Bruton's tyrosine kinase (BTK) with great efficacy in chronic lymphocytic leukemia (CLL). Common side effects like atrial fibrillation (AF), bleeding and infections might be caused by ibrutinib's inhibition of other kinases in non-B cells. Five-year follow-up of plasma biomarkers by proximity extension assay and immune cell numbers by flow cytometry during ibrutinib treatment revealed that 86 of the 265 investigated plasma biomarkers significantly changed during treatment, 74 of which decreased. Among the 12 markers that increased, 6 are associated with cardiovascular diseases and therefore potentially involved in ibrutinib-induced AF. Comparison between healthy donors and X-linked agammaglobulinemia (XLA) patients, who have nonfunctional BTK and essentially lack B cells, showed indicative changes in 53 of the 265 biomarkers while none differed significantly. Hence, neither B cells nor BTK-dependent pathways in other cells seem to influence the levels of the studied plasma biomarkers in healthy donors. Regarding immune cells, the absolute number of T cells, including subsets, decreased, paralleling the decreasing tumor burden. T helper 1 (Th1) cell numbers dropped strongly, while Th2 cells remained relatively stable, causing Th2-skewing. Thus, long-term ibrutinib treatment has a profound impact on the plasma proteome and immune cells in patients with CLL.
Identifiants
pubmed: 33912812
doi: 10.1097/HS9.0000000000000564
pmc: PMC8078281
doi:
Types de publication
Journal Article
Langues
eng
Pagination
e564Informations de copyright
Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Hematology Association.
Références
ChemMedChem. 2007 Jan;2(1):58-61
pubmed: 17154430
Cancer Res. 2016 Apr 15;76(8):2125-36
pubmed: 26880800
Arterioscler Thromb Vasc Biol. 2014 Dec;34(12):2695-9
pubmed: 25341801
Transgenic Res. 2013 Dec;22(6):1179-89
pubmed: 23921644
Nature. 1993 Jan 21;361(6409):226-33
pubmed: 8380905
Atherosclerosis. 2018 Jun;273:1-7
pubmed: 29649633
Cardiovasc Res. 2007 Mar 1;73(4):783-93
pubmed: 17208206
Blood. 2013 Feb 28;121(9):1612-21
pubmed: 23247726
Eur J Immunol. 2006 May;36(5):1285-95
pubmed: 16619289
Blood. 2005 Sep 15;106(6):2018-25
pubmed: 15914560
Eur J Immunol. 2001 Jun;31(6):1927-34
pubmed: 11433390
Blood. 2015 Nov 5;126(19):2213-9
pubmed: 26337493
Int J Lab Hematol. 2020 Jun;42 Suppl 1:113-120
pubmed: 32543070
Blood. 2016 Dec 22;128(25):2899-2908
pubmed: 27802969
PLoS One. 2014 Apr 22;9(4):e95192
pubmed: 24755770
Int J Mol Med. 2008 Feb;21(2):233-8
pubmed: 18204790
Clin Exp Immunol. 2003 Jul;133(1):115-22
pubmed: 12823285
Science. 2019 Dec 20;366(6472):
pubmed: 31857451
Proc Natl Acad Sci U S A. 2002 May 14;99(10):6955-60
pubmed: 12011454
Adv Immunol. 1995;59:135-223
pubmed: 7484460
Blood Adv. 2020 Jun 9;4(11):2439-2450
pubmed: 32492159
J Heart Lung Transplant. 2008 Jul;27(7):701-9
pubmed: 18582797
Blood. 2019 Mar 7;133(10):1011-1019
pubmed: 30530801
Leukemia. 2016 Apr;30(4):833-43
pubmed: 26582643
Proc Natl Acad Sci U S A. 2010 Jul 20;107(29):13075-80
pubmed: 20615965
J Am Coll Cardiol. 2019 Oct 1;74(13):1667-1678
pubmed: 31558250
Science. 2019 Feb 15;363(6428):748-753
pubmed: 30765568
Blood. 2018 Jun 21;131(25):2745-2760
pubmed: 29540348
J Clin Immunol. 2012 Oct;32(5):967-74
pubmed: 22665224
Eur Heart J. 2020 Mar 7;41(10):1123-1131
pubmed: 31713590
Br J Haematol. 2018 Oct;183(2):212-224
pubmed: 30125946
Haematologica. 2017 Mar;102(3):562-572
pubmed: 27927767
Haematologica. 2017 Oct;102(10):e397-e399
pubmed: 28659336
Cell. 1993 Jan 29;72(2):279-90
pubmed: 8425221
Arterioscler Thromb Vasc Biol. 2015 Dec;35(12):2496-507
pubmed: 26515415
Circ Arrhythm Electrophysiol. 2019 Apr;12(4):e007212
pubmed: 30894015
Blood Cells Mol Dis. 2004 Jan-Feb;32(1):52-7
pubmed: 14757413
Blood. 2012 Mar 15;119(11):2590-4
pubmed: 22279054
Clin Cancer Res. 2016 Apr 1;22(7):1572-82
pubmed: 26660519
J Clin Invest. 2017 Aug 1;127(8):3052-3064
pubmed: 28714866
Mol Med Rep. 2017 Nov;16(5):5823-5832
pubmed: 28849223
J Exp Med. 1990 Mar 1;171(3):659-66
pubmed: 2137853
Clin Immunol. 2019 Mar;200:39-42
pubmed: 30690192
PLoS One. 2012;7(7):e40243
pubmed: 22792252
Oncoimmunology. 2016 Mar 10;5(6):e1151592
pubmed: 27471620
Exp Cell Res. 2020 May 15;390(2):111950
pubmed: 32188578
Oncoimmunology. 2018 Feb 20;7(6):e1432328
pubmed: 29872562
Life Sci. 2017 Dec 15;191:253-258
pubmed: 29080693
Eur Heart J. 2019 Apr 21;40(16):1268-1276
pubmed: 30615112
Leuk Res. 2019 Dec;87:106233
pubmed: 31639635
Immunity. 2007 Jan;26(1):93-104
pubmed: 17239630
Blood. 2014 Mar 20;123(12):1957-60
pubmed: 24652965
J Immunol. 2017 Feb 15;198(4):1740-1747
pubmed: 28077600
Clin Cancer Res. 2014 Feb 1;20(3):548-56
pubmed: 24323900
EMBO Mol Med. 2017 Sep;9(9):1279-1293
pubmed: 28774883
Leukemia. 2017 Jul;31(7):1555-1561
pubmed: 27904140
Nat Commun. 2018 Feb 26;9(1):816
pubmed: 29483579
J Immunol. 1994 Jan 15;152(2):557-65
pubmed: 8283037
Biomark Med. 2017 Mar;11(3):229-237
pubmed: 28157385
Scand J Immunol. 2015 Sep;82(3):208-17
pubmed: 26111359
Pediatr Res. 2002 Feb;51(2):159-68
pubmed: 11809909
Int J Mol Sci. 2019 Dec 20;21(1):
pubmed: 31861854
Blood. 2014 Jul 31;124(5):750-60
pubmed: 24850760
Oncotarget. 2017 May 23;8(21):34661-34669
pubmed: 28416773
Leuk Res. 2002 Jul;26(7):657-60
pubmed: 12008083
Cytometry. 2000 Jun 15;42(3):188-95
pubmed: 10861692
Leukemia. 2018 Apr;32(4):960-970
pubmed: 28972595
Clin Cancer Res. 2015 Oct 15;21(20):4642-51
pubmed: 26089373
Eur J Immunol. 1993 Dec;23(12):3109-14
pubmed: 8258324
Blood. 2013 Oct 10;122(15):2539-49
pubmed: 23886836
Scand Cardiovasc J. 2016;50(1):36-41
pubmed: 26441035