Skin mesenchymal niches maintain and protect AML-initiating stem cells.
Journal
The Journal of experimental medicine
ISSN: 1540-9538
Titre abrégé: J Exp Med
Pays: United States
ID NLM: 2985109R
Informations de publication
Date de publication:
02 10 2023
02 10 2023
Historique:
received:
01
06
2022
revised:
10
05
2023
accepted:
29
06
2023
pmc-release:
26
01
2024
medline:
31
7
2023
pubmed:
30
7
2023
entrez:
30
7
2023
Statut:
ppublish
Résumé
Leukemia cutis or leukemic cell infiltration in skin is one of the common extramedullary manifestations of acute myeloid leukemia (AML) and signifies a poorer prognosis. However, its pathogenesis and maintenance remain understudied. Here, we report massive AML cell infiltration in the skin in a transplantation-induced MLL-AF9 AML mouse model. These AML cells could regenerate AML after transplantation. Prospective niche characterization revealed that skin harbored mesenchymal progenitor cells (MPCs) with a similar phenotype as BM mesenchymal stem cells. These skin MPCs protected AML-initiating stem cells (LSCs) from chemotherapy in vitro partially via mitochondrial transfer. Furthermore, Lama4 deletion in skin MPCs promoted AML LSC proliferation and chemoresistance. Importantly, more chemoresistant AML LSCs appeared to be retained in Lama4-/- mouse skin after cytarabine treatment. Our study reveals the characteristics and previously unrecognized roles of skin mesenchymal niches in maintaining and protecting AML LSCs during chemotherapy, meriting future exploration of their impact on AML relapse.
Identifiants
pubmed: 37516911
pii: 276131
doi: 10.1084/jem.20220953
pmc: PMC10373345
pii:
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2023 Sandhow et al.
Références
J Immunol Methods. 2009 Aug 15;347(1-2):70-8
pubmed: 19567251
Blood. 2016 Jul 14;128(2):253-64
pubmed: 27257182
Nat Cell Biol. 2001 Sep;3(9):778-84
pubmed: 11533656
Nat Cell Biol. 2020 Jan;22(1):7-17
pubmed: 31907409
Dev Cell. 2011 Aug 16;21(2):193-215
pubmed: 21839917
Mol Cancer Ther. 2008 Jan;7(1):48-58
pubmed: 18202009
J Exp Med. 2005 Jun 6;201(11):1781-91
pubmed: 15928197
JAMA Dermatol. 2019 Jul 1;155(7):826-832
pubmed: 30969325
Cancer Cell. 2015 May 11;27(5):671-81
pubmed: 25965572
Oncotarget. 2015 Jun 20;6(17):14905-12
pubmed: 25915157
Hemasphere. 2018 Oct;2(5):e141
pubmed: 30887005
Blood. 2022 May 19;139(20):3040-3057
pubmed: 34958665
Nature. 2003 Oct 23;425(6960):841-6
pubmed: 14574413
Haematologica. 2020 Mar;105(3):e102-e106
pubmed: 31296580
Oncogene. 2017 Aug 10;36(32):4619-4628
pubmed: 28368400
Methods Mol Biol. 2008;430:143-57
pubmed: 18370297
J Exp Med. 2009 Oct 26;206(11):2483-96
pubmed: 19841085
Eur J Haematol. 2003 Feb;70(2):106-14
pubmed: 12581192
Mol Cell Biol. 2013 Feb;33(4):661-77
pubmed: 23184664
Cell Stem Cell. 2016 Jul 7;19(1):23-37
pubmed: 27374788
Blood. 2003 Feb 1;101(3):877-85
pubmed: 12393739
Leukemia. 2018 Mar;32(3):588-596
pubmed: 28819278
Cancer Discov. 2017 Jul;7(7):716-735
pubmed: 28416471
Cell Stem Cell. 2014 Sep 4;15(3):365-375
pubmed: 25017722
Cytotherapy. 2019 Oct;21(10):1019-1024
pubmed: 31526643
J Invest Dermatol. 2012 Mar;132(3 Pt 1):563-74
pubmed: 22048731
Cell Rep. 2013 Sep 12;4(5):1022-34
pubmed: 24012753
Nucleic Acids Res. 2013 May 1;41(10):e108
pubmed: 23558742
Cancer Res. 2015 Jun 1;75(11):2222-31
pubmed: 25791383
Blood Adv. 2018 Mar 13;2(5):534-548
pubmed: 29514790
Blood. 2011 Oct 6;118(14):3785-93
pubmed: 21795742
J Clin Invest. 2007 Apr;117(4):1049-57
pubmed: 17380207
Cancer Cell. 2006 Oct;10(4):257-68
pubmed: 17045204
Stem Cells. 2018 Oct;36(10):1617-1629
pubmed: 30004606
Nature. 2013 Mar 14;495(7440):227-30
pubmed: 23434756
Nature. 2016 Nov 10;539(7628):304-308
pubmed: 27783593
Nature. 2010 Apr 8;464(7290):852-7
pubmed: 20305640
Oncotarget. 2016 Apr 26;7(17):24436-54
pubmed: 27027438
J Exp Med. 2013 Jul 1;210(7):1351-67
pubmed: 23776077
Matrix Biol. 2018 Apr;67:47-62
pubmed: 29360499
Cell. 2019 Jun 13;177(7):1915-1932.e16
pubmed: 31130381
Mol Cell Biol. 2002 Feb;22(4):1194-202
pubmed: 11809810
Blood Adv. 2018 Jun 26;2(12):1480-1494
pubmed: 29945938
J Biol Chem. 2012 Jul 27;287(31):25795-807
pubmed: 22654106
Blood. 2017 Oct 5;130(14):1649-1660
pubmed: 28733324
Cancer Res. 2011 Jun 1;71(11):3831-40
pubmed: 21512135
Nat Methods. 2008 Jul;5(7):621-8
pubmed: 18516045
Cell. 2004 Jul 23;118(2):149-61
pubmed: 15260986
Blood. 2013 Mar 7;121(10):1824-38
pubmed: 23299311
Blood. 2010 Feb 4;115(5):957-64
pubmed: 19897586
Annu Rev Pathol. 2016 May 23;11:555-81
pubmed: 27193455
Cell Stem Cell. 2018 Jan 4;22(1):64-77.e6
pubmed: 29276143
Immunity. 2010 Sep 24;33(3):387-99
pubmed: 20850355
Haematologica. 2018 Mar;103(3):447-455
pubmed: 29284680
Cutis. 2018 Oct;102(4):266;271;272
pubmed: 30489552
Nature. 2016 Apr 21;532(7599):380-4
pubmed: 27074508
J Immunol. 2008 Feb 15;180(4):2045-53
pubmed: 18250409
Methods Mol Biol. 2013;989:217-33
pubmed: 23483398
Cell Stem Cell. 2013 Sep 5;13(3):285-99
pubmed: 23850243
Cell Metab. 2020 Nov 3;32(5):829-843.e9
pubmed: 32966766
Nat Chem Biol. 2013 Dec;9(12):840-848
pubmed: 24161946