Inflammatory recruitment of healthy hematopoietic stem and progenitor cells in the acute myeloid leukemia niche.
Journal
Leukemia
ISSN: 1476-5551
Titre abrégé: Leukemia
Pays: England
ID NLM: 8704895
Informations de publication
Date de publication:
16 Jan 2024
16 Jan 2024
Historique:
received:
03
08
2023
accepted:
04
01
2024
revised:
21
12
2023
medline:
17
1
2024
pubmed:
17
1
2024
entrez:
16
1
2024
Statut:
aheadofprint
Résumé
Inflammation in the bone marrow (BM) microenvironment is a constitutive component of leukemogenesis in acute myeloid leukemia (AML). Current evidence suggests that both leukemic blasts and stroma secrete proinflammatory factors that actively suppress the function of healthy hematopoietic stem and progenitor cells (HSPCs). HSPCs are also cellular components of the innate immune system, and we reasoned that they may actively propagate the inflammation in the leukemic niche. In two separate congenic models of AML we confirm by evaluation of the BM plasma secretome and HSPC-selective single-cell RNA sequencing (scRNA-Seq) that multipotent progenitors and long-lived stem cells adopt inflammatory gene expression programs, even at low leukemic infiltration of the BM. In particular, we observe interferon gamma (IFN-γ) pathway activation, along with secretion of its chemokine target, CXCL10. We show that AML-derived nanometer-sized extracellular vesicles (EV
Identifiants
pubmed: 38228679
doi: 10.1038/s41375-024-02136-7
pii: 10.1038/s41375-024-02136-7
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Alex's Lemonade Stand Foundation for Childhood Cancer (Alex's Lemonade Stand Foundation)
ID : 21-23996
Informations de copyright
© 2024. The Author(s).
Références
De Kouchkovsky I, Abdul-Hay M. Acute myeloid leukemia: a comprehensive review and 2016 update. Blood Cancer J 2016;6:e441.
pubmed: 27367478
pmcid: 5030376
doi: 10.1038/bcj.2016.50
Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2022. CA: A Cancer J Clin. 2022;72:7–33.
Hornick NI, Doron B, Abdelhamed S, Huan J, Harrington CA, Shen R, et al. AML suppresses hematopoiesis by releasing exosomes that contain microRNAs targeting c-MYB. Sci Signal. 2016;9:ra88.
pubmed: 27601730
doi: 10.1126/scisignal.aaf2797
Abdelhamed S, Butler JT, Doron B, Halse A, Nemecek E, Wilmarth PA, et al. Extracellular vesicles impose quiescence on residual hematopoietic stem cells in the leukemic niche. EMBO Rep. 2019;20:e47546.
pubmed: 31267709
pmcid: 6607014
doi: 10.15252/embr.201847546
Binder S, Luciano M, Horejs-Hoeck J. The cytokine network in acute myeloid leukemia (AML): A focus on pro- and anti-inflammatory mediators. Cytokine Growth Factor Rev. 2018;43:8–15.
pubmed: 30181021
doi: 10.1016/j.cytogfr.2018.08.004
Kristinsson SY, Björkholm M, Hultcrantz M, Derolf ÅR, Landgren O, Goldin LR. Chronic immune stimulation might act as a trigger for the development of acute myeloid leukemia or myelodysplastic syndromes. J Clin Oncol. 2011;29:2897–903.
pubmed: 21690473
pmcid: 3138717
doi: 10.1200/JCO.2011.34.8540
Pietras EM. Inflammation: a key regulator of hematopoietic stem cell fate in health and disease. Blood .2017;130:1693–8.
pubmed: 28874349
pmcid: 5639485
doi: 10.1182/blood-2017-06-780882
Schepers K, Campbell TB, Passegué E. Normal and leukemic stem cell niches: insights and therapeutic opportunities. Cell Stem Cell. 2015;16:254–67.
pubmed: 25748932
pmcid: 4391962
doi: 10.1016/j.stem.2015.02.014
Zhang TY, Dutta R, Benard B, Zhao F, Yin R, Majeti R. IL-6 blockade reverses bone marrow failure induced by human acute myeloid leukemia. Sci Transl Med. 2020;12:eaax5104.
pubmed: 32269167
pmcid: 7266679
doi: 10.1126/scitranslmed.aax5104
Zhao JL, Ma C, O’Connell MR, Mehta A, DiLoreto R, Heath JR, et al. Conversion of danger signals into cytokine signals by hematopoietic stem and progenitor cells for regulation of stress-induced hematopoiesis. Cell Stem Cell. 2014;14:445–59.
pubmed: 24561084
pmcid: 4119790
doi: 10.1016/j.stem.2014.01.007
Guzman ML, Neering SJ, Upchurch D, Grimes B, Howard DS, Rizzieri DA, et al. Nuclear factor-κB is constitutively activated in primitive human acute myelogenous leukemia cells. Blood, J Am Soc Hematol 2001;98:2301–7.
Carey A, Edwards DK, Eide CA, Newell L, Traer E, Medeiros BC, et al. Identification of Interleukin-1 by Functional Screening as a Key Mediator of Cellular Expansion and Disease Progression in Acute Myeloid Leukemia. Cell Rep. 2017;18:3204–18.
pubmed: 28355571
pmcid: 5437102
doi: 10.1016/j.celrep.2017.03.018
Zambetti NA, Ping Z, Chen S, Kenswil KJ, Mylona MA, Sanders MA, et al. Mesenchymal inflammation drives genotoxic stress in hematopoietic stem cells and predicts disease evolution in human pre-leukemia. Cell Stem Cell. 2016;19:613–27.
pubmed: 27666011
doi: 10.1016/j.stem.2016.08.021
Essers MAG, Offner S, Blanco-Bose WE, Waibler Z, Kalinke U, Duchosal MA, et al. IFNα activates dormant haematopoietic stem cells in vivo. Nature .2009;458:904.
pubmed: 19212321
doi: 10.1038/nature07815
Butler JT, Abdelhamed S, Kurre P. Extracellular vesicles in the hematopoietic microenvironment. Haematologica .2018;103:382–94.
pubmed: 29439185
pmcid: 5830368
doi: 10.3324/haematol.2017.183335
Ortiz A, Gui J, Zahedi F, Yu P, Cho C, Bhattacharya S, et al. An interferon-driven oxysterol-based defense against tumor-derived extracellular vesicles. Cancer Cell 2019;35:33–45. e6.
pubmed: 30645975
pmcid: 6336114
doi: 10.1016/j.ccell.2018.12.001
Kumar B, Garcia M, Weng L, Jung X, Murakami JL, Hu X, et al. Acute myeloid leukemia transforms the bone marrow niche into a leukemia-permissive microenvironment through exosome secretion. Leukemia .2018;32:575–87.
pubmed: 28816238
doi: 10.1038/leu.2017.259
Doron B, Abdelhamed S, Butler JT, Hashmi SK, Horton TM, Kurre P. Transmissible ER stress reconfigures the AML bone marrow compartment. Leukemia. 2019;33:918–30.
pubmed: 30206307
doi: 10.1038/s41375-018-0254-2
Pietras EM, Lakshminarasimhan R, Techner J-M, Fong S, Flach J, Binnewies M, et al. Re-entry into quiescence protects hematopoietic stem cells from the killing effect of chronic exposure to type I interferons. J Exp Med. 2014;211:245–62.
pubmed: 24493802
pmcid: 3920566
doi: 10.1084/jem.20131043
Ju J-M, Jung MH, Nam G, Kim W, Oh S, Kim HD, et al. Escape from thymic deletion and anti-leukemic effects of T cells specific for hematopoietic cell-restricted antigen. Nat Commun. 2018;9:225.
pubmed: 29335408
pmcid: 5768767
doi: 10.1038/s41467-017-02665-z
Deng M, Gui X, Kim J, Xie L, Chen W, Li Z, et al. LILRB4 signalling in leukaemia cells mediates T cell suppression and tumour infiltration. Nature 2018;562:605–9.
pubmed: 30333625
pmcid: 6296374
doi: 10.1038/s41586-018-0615-z
Yan F, Shen N, Pang JX, Zhang YW, Rao EY, Bode AM, et al. Fatty acid-binding protein FABP4 mechanistically links obesity with aggressive AML by enhancing aberrant DNA methylation in AML cells. Leukemia .2017;31:1434–42.
pubmed: 27885273
doi: 10.1038/leu.2016.349
Li J-M, Petersen CT, Li J-X, Panjwani R, Chandra DJ, Giver CR, et al. Modulation of immune checkpoints and graft-versus-leukemia in allogeneic transplants by antagonizing vasoactive intestinal peptide signaling. Cancer Res. 2016;76:6802–15.
pubmed: 27671676
pmcid: 5135614
doi: 10.1158/0008-5472.CAN-16-0427
Curran E, Chen X, Corrales L, Kline DE, others. STING pathway activation stimulates potent immunity against acute myeloid leukemia. Cell Rep. (2016).
Ratajczak M, Adamiak M, Deptala A, Domagala-Kulawik J, Ratajczak J, Kucia M. Myeloablative Conditioning for Transplantation Induces State of Sterile Inflammation in the Bone Marrow: Implications for Optimizing Homing and Engraftment of Hematopoietic Stem Cells. Antioxidant & Redox Signaling. 2022;37:1254–65.
doi: 10.1089/ars.2022.0042
Pietras EM, Reynaud D, Kang Y-A, Carlin D, Calero-Nieto FJ, Leavitt AD, et al. Functionally distinct subsets of lineage-biased multipotent progenitors control blood production in normal and regenerative conditions. Cell Stem Cell. 2015;17:35–46.
pubmed: 26095048
pmcid: 4542150
doi: 10.1016/j.stem.2015.05.003
Krivtsov AV, Twomey D, Feng Z, Stubbs MC, Wang Y, Faber J, et al. Transformation from committed progenitor to leukaemia stem cell initiated by MLL–AF9. Nature. 2006;442:818–22.
pubmed: 16862118
doi: 10.1038/nature04980
Bernt KM, Zhu N, Sinha AU, Vempati S, Faber J, Krivtsov AV, et al. MLL-rearranged leukemia is dependent on aberrant H3K79 methylation by DOT1L. Cancer Cell 2011;20:66–78.
pubmed: 21741597
pmcid: 3329803
doi: 10.1016/j.ccr.2011.06.010
Stavropoulou V, Kaspar S, Brault L, Sanders MA, Juge S, Morettini S, et al. MLL-AF9 expression in hematopoietic stem cells drives a highly invasive AML expressing EMT-related genes linked to poor outcome. Cancer Cell. 2016;30:43–58.
pubmed: 27344946
doi: 10.1016/j.ccell.2016.05.011
Chen X, Burkhardt DB, Hartman AA, Hu X, Eastman AE, Sun C, et al. MLL-AF9 initiates transformation from fast-proliferating myeloid progenitors. Nat Commun. 2019;10:5767.
pubmed: 31852898
pmcid: 6920141
doi: 10.1038/s41467-019-13666-5
Kelly-Scumpia KM, Scumpia PO, Delano MJ, Weinstein JS, Cuenca AG, Wynn JL, et al. Type I interferon signaling in hematopoietic cells is required for survival in mouse polymicrobial sepsis by regulating CXCL10. J Exp Med. 2010;207:319–26.
pubmed: 20071504
pmcid: 2822595
doi: 10.1084/jem.20091959
Baldridge MT, King KY, Boles NC, Weksberg DC, Goodell MA. Quiescent haematopoietic stem cells are activated by IFN-γ in response to chronic infection. Nature. 2010;465:793–7.
pubmed: 20535209
pmcid: 2935898
doi: 10.1038/nature09135
Kanayama M, Izumi Y, Yamauchi Y, Kuroda S, Shin T, Ishikawa S, et al. CD86-based analysis enables observation of bona fide hematopoietic responses. Blood. 2020;136:1144–54.
pubmed: 32438398
doi: 10.1182/blood.2020004923
Cai Z, Kotzin JJ, Ramdas B, Chen S, Nelanuthala S, Palam LR, et al. Inhibition of inflammatory signaling in Tet2 mutant preleukemic cells mitigates stress-induced abnormalities and clonal hematopoiesis. Cell Stem Cell 2018;23:833–49.
pubmed: 30526882
pmcid: 6317370
doi: 10.1016/j.stem.2018.10.013
Welner RS, Amabile G, Bararia D, Czibere A, Yang H, Zhang H, et al. Treatment of chronic myelogenous leukemia by blocking cytokine alterations found in normal stem and progenitor cells. Cancer Cell 2015;27:671–81.
pubmed: 25965572
pmcid: 4447336
doi: 10.1016/j.ccell.2015.04.004
Kleppe M, Kwak M, Koppikar P, Riester M, Keller M, Bastian L, et al. JAK–STAT pathway activation in malignant and nonmalignant cells contributes to MPN pathogenesis and therapeutic responseJAK–STAT pathway activation in malignant and nonmalignant cells in MPN. Cancer Discov. 2015;5:316–31.
pubmed: 25572172
pmcid: 4355105
doi: 10.1158/2159-8290.CD-14-0736
Holicek P, Truxova I, Rakova J, Salek C, Hensler M, Kovar M, et al. Type I interferon signaling in malignant blasts contributes to treatment efficacy in AML patients. Cell Death Dis. 2023;14:209.
pubmed: 36964168
pmcid: 10039058
doi: 10.1038/s41419-023-05728-w
de Laval B, Maurizio J, Kandalla P, Brisou G, Simonnet L, Huber C, et al. C/EBPβ-dependent epigenetic memory induces trained immunity in hematopoietic stem cells. Cell Stem Cell. 2020;26:657–74.
pubmed: 32169166
doi: 10.1016/j.stem.2020.01.017
Abdelhamed S, Butler JT, Jung S, Chen D-W, Jenkins G, Gao L, et al. Rational biomarker development for the early and minimally invasive monitoring of AML. Blood Adv. 2021;5:4515–20.
pubmed: 34587228
pmcid: 8579272
doi: 10.1182/bloodadvances.2021004621
Bogeska R, Mikecin A-M, Kaschutnig P, Fawaz M, Büchler-Schäff M, Le D, et al. Inflammatory exposure drives long-lived impairment of hematopoietic stem cell self-renewal activity and accelerated aging. Cell Stem Cell. 2022;29:1273–84.e8.
pubmed: 35858618
pmcid: 9357150
doi: 10.1016/j.stem.2022.06.012
Schepers K, Pietras EM, Reynaud D, Flach J, Binnewies M, Garg T, et al. Myeloproliferative neoplasia remodels the endosteal bone marrow niche into a self-reinforcing leukemic niche. Cell Stem Cell. 2013;13:285–99.
pubmed: 23850243
pmcid: 3769504
doi: 10.1016/j.stem.2013.06.009
Miraki-Moud F, Anjos-Afonso F, Hodby KA, Griessinger E, Rosignoli G, Lillington D, et al. Acute myeloid leukemia does not deplete normal hematopoietic stem cells but induces cytopenias by impeding their differentiation. Proc Natl Acad Sci. 2013;110:13576–81.
pubmed: 23901108
pmcid: 3746910
doi: 10.1073/pnas.1301891110
Boyd AL, Reid JC, Salci KR, Aslostovar L, Benoit YD, Shapovalova Z, et al. Acute myeloid leukaemia disrupts endogenous myelo-erythropoiesis by compromising the adipocyte bone marrow niche. Nat Cell Biol. 2017;19:1336–47.
pubmed: 29035359
doi: 10.1038/ncb3625
Akinduro O, Weber TS, Ang H, Haltalli M, Ruivo N, Duarte D, et al. Proliferation dynamics of acute myeloid leukaemia and haematopoietic progenitors competing for bone marrow space. Nat Commun. 2018;9:519.
pubmed: 29410432
pmcid: 5802720
doi: 10.1038/s41467-017-02376-5
Corces-Zimmerman MR, Hong W-J, Weissman IL, Medeiros BC, Majeti R. Preleukemic mutations in human acute myeloid leukemia affect epigenetic regulators and persist in remission. Proc Natl Acad Sci. 2014;111:2548–53.
pubmed: 24550281
pmcid: 3932921
doi: 10.1073/pnas.1324297111
Caiado F, Pietras EM, Manz MG. Inflammation as a regulator of hematopoietic stem cell function in disease, aging, and clonal selection. J Exp Med. 2021;218:e20201541.
pubmed: 34129016
pmcid: 8210622
doi: 10.1084/jem.20201541
Hormaechea-Agulla D, Matatall KA, Le DT, Kain B, Long X, Kus P, et al. Chronic infection drives Dnmt3a-loss-of-function clonal hematopoiesis via IFNγ signaling. Cell Stem Cell. 2021;28:1428–42.
pubmed: 33743191
pmcid: 8349829
doi: 10.1016/j.stem.2021.03.002
Matatall KA, Jeong M, Chen S, Sun D, Chen F, Mo Q, et al. Chronic infection depletes hematopoietic stem cells through stress-induced terminal differentiation. Cell Rep. 2016;17:2584–95.
pubmed: 27926863
pmcid: 5161248
doi: 10.1016/j.celrep.2016.11.031
Tall AR, Fuster JJ. Clonal hematopoiesis in cardiovascular disease and therapeutic implications. Nat Cardiovasc Res. 2022;1:116–24.
pubmed: 36337911
pmcid: 9631799
doi: 10.1038/s44161-021-00015-3
Gómez AM, Martínez C, González M, Luque A, Melen GJ, Martínez J, et al. Chemokines and relapses in childhood acute lymphoblastic leukemia: a role in migration and in resistance to antileukemic drugs. Blood Cells, Mol, Dis. 2015;55:220–7.
pubmed: 26227851
doi: 10.1016/j.bcmd.2015.07.001
Lee Y, Chittezhath M, André V, Zhao H, Poidinger M, Biondi A, et al. Protumoral role of monocytes in human B-cell precursor acute lymphoblastic leukemia: involvement of the chemokine CXCL10. Blood, J Am Soc Hematol. 2012;119:227–37.
Sarris AH, Broxmeyer HE, Wirthmueller U, Karasavvas N, Cooper S, Lu L, et al. Human interferon-inducible protein 10: expression and purification of recombinant protein demonstrate inhibition of early human hematopoietic progenitors. J Exp Med. 1993;178:1127–32.
pubmed: 8350051
doi: 10.1084/jem.178.3.1127
Aldinucci D, Poletto D, Nanni P, Degan M, Rupolo M, Pinto A, et al. CD40L induces proliferation, self-renewal, rescue from apoptosis, and production of cytokines by CD40-expressing AML blasts. Exp Hematol. 2002;30:1283–92.
pubmed: 12423681
doi: 10.1016/S0301-472X(02)00921-9
Argiropoulos B, Palmqvist L, Yung E, Kuchenbauer F, Heuser M, Sly LM, et al. Linkage of Meis1 leukemogenic activity to multiple downstream effectors including Trib2 and Ccl3. Exp Hematol. 2008;36:845–59.
pubmed: 18375036
doi: 10.1016/j.exphem.2008.02.011
Kornblau SM, Mccue D, Singh N, Chen W, Estrov Z, Coombes KR. Recurrent expression signatures of cytokines and chemokines are present and are independently prognostic in acute myelogenous leukemia and myelodysplasia. Blood .2010;116:4251–61.
pubmed: 20679526
pmcid: 4081283
doi: 10.1182/blood-2010-01-262071
Vijay V, Miller R, Vue GS, Pezeshkian MB, Maywood M, Ast AM, et al. Interleukin-8 blockade prevents activated endothelial cell mediated proliferation and chemoresistance of acute myeloid leukemia. Leuk Res. 2019;84:106180.
pubmed: 31299413
pmcid: 6857733
doi: 10.1016/j.leukres.2019.106180
Vadakekolathu J, Minden MD, Hood T, Church SE, Reeder S, Altmann H, et al. Immune landscapes predict chemotherapy resistance and immunotherapy response in acute myeloid leukemia. Sci Transl Med. 2020;12:eaaz0463.
pubmed: 32493790
pmcid: 7427158
doi: 10.1126/scitranslmed.aaz0463
Stevens AM, Miller JM, Munoz JO, Gaikwad AS, Redell MS. Interleukin-6 levels predict event-free survival in pediatric AML and suggest a mechanism of chemotherapy resistance. Blood Adv 2017;1:1387–97.
pubmed: 29296780
pmcid: 5727855
doi: 10.1182/bloodadvances.2017007856
Lasry A, Nadorp B, Fornerod M, Nicolet D, Wu H, Walker CJ, et al. An inflammatory state remodels the immune microenvironment and improves risk stratification in acute myeloid leukemia. Nature Cancer. 2022;4:27–42.
Bertoli S, Picard M, Bérard E, Griessinger E, Larrue C, Mouchel PL, et al. Dexamethasone in hyperleukocytic acute myeloid leukemia. Haematologica. 2018;103:988–98.
pubmed: 29519869
pmcid: 6058767
doi: 10.3324/haematol.2017.184267