{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T04:27:32Z","timestamp":1773462452169,"version":"3.50.1"},"reference-count":63,"publisher":"American Society of Hematology","issue":"10","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,5,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Acute myeloid leukemia (AML) is a blood cancer of the myeloid lineage. Its prognosis remains poor, highlighting the need for new therapeutic and precision medicine approaches. AML symptoms often include cytopenias linked to loss of healthy hematopoietic stem and progenitor cells (HSPCs). The mechanisms behind HSPC decline are complex and still poorly understood. Here, intravital microscopy (IVM) of a well-established experimental model of AML allows direct observation of the interactions between healthy and malignant cells in the bone marrow (BM), suggesting that physical dislodgment of healthy cells by AML through damaged vasculature may play an important role. Multiple matrix metalloproteinases (MMPs), known to remodel extracellular matrix, are expressed by AML cells and the BM microenvironment. We reason MMPs could be involved in cell displacement and vascular leakiness; therefore, we evaluate the therapeutic potential of MMP pharmacological inhibition using the broad-spectrum inhibitor prinomastat. IVM analyses of prinomastat-treated mice reveal reduced vascular permeability and healthy cell clusters in circulation and lower AML infiltration, proliferation, and cell migration. Furthermore, treated mice have increased retention of healthy HSPCs in the BM and increased survival following chemotherapy. Analysis of a human AML transcriptomic database reveals widespread MMP deregulation, and human AML cells show susceptibility to MMP inhibition. Overall, our results suggest that MMP inhibition could be a promising complementary therapy to reduce AML growth and limit HSPC loss and BM vascular damage caused by MLL-AF9 and possibly other AML subtypes.<\/jats:p>","DOI":"10.1182\/bloodadvances.2021004321","type":"journal-article","created":{"date-parts":[[2022,2,14]],"date-time":"2022-02-14T22:04:02Z","timestamp":1644876242000},"page":"3126-3141","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":22,"title":["Metalloproteinase inhibition reduces AML growth, prevents stem cell loss, and improves chemotherapy effectiveness"],"prefix":"10.1182","volume":"6","author":[{"given":"Chiara","family":"Pirillo","sequence":"first","affiliation":[{"name":"Department of Life Sciences, Sir Alexander Fleming Building, Imperial College London, London, United Kingdom;"},{"name":"The Francis Crick Institute, London, United Kingdom;"},{"name":"Beatson Institute for Cancer Research, Glasgow, United Kingdom;"}]},{"given":"Flora","family":"Birch","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, Sir Alexander Fleming Building, Imperial College London, London, United Kingdom;"},{"name":"The Francis Crick Institute, London, United Kingdom;"},{"name":"Centre for Haematology, Department of Immunology and Inflammation, Imperial College London, London, United Kingdom;"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7599-3535","authenticated-orcid":false,"given":"Floriane S.","family":"Tissot","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, Sir Alexander Fleming Building, Imperial College London, London, United Kingdom;"},{"name":"The Francis Crick Institute, London, United Kingdom;"},{"name":"Centre for Haematology, Department of Immunology and Inflammation, Imperial College London, London, United Kingdom;"}]},{"given":"Sara Gonzalez","family":"Anton","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, Sir Alexander Fleming Building, Imperial College London, London, United Kingdom;"},{"name":"The Francis Crick Institute, London, United Kingdom;"},{"name":"Centre for Haematology, Department of Immunology and Inflammation, Imperial College London, London, United Kingdom;"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0886-4466","authenticated-orcid":false,"given":"Myriam","family":"Haltalli","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, Sir Alexander Fleming Building, Imperial College London, London, United Kingdom;"},{"name":"The Francis Crick Institute, London, United Kingdom;"}]},{"given":"Valentina","family":"Tini","sequence":"additional","affiliation":[{"name":"Institute of Haematology, Centro di Ricerca Emato-Oncologica (CREO), University of Perugia, Perugia, Italy;"}]},{"given":"Isabella","family":"Kong","sequence":"additional","affiliation":[{"name":"The Walter and Eliza Hall Institute of Medical Research, University of Melbourne, Parkville, VIC, Australia;"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7639-3662","authenticated-orcid":false,"given":"C\u00e9cile","family":"Piot","sequence":"additional","affiliation":[{"name":"The Francis Crick Institute, London, United Kingdom;"}]},{"given":"Ben","family":"Partridge","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, Imperial College London, London, United Kingdom;"}]},{"given":"Constandina","family":"Pospori","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, Sir Alexander Fleming Building, Imperial College London, London, United Kingdom;"},{"name":"The Francis Crick Institute, London, United Kingdom;"},{"name":"Centre for Haematology, Department of Immunology and Inflammation, Imperial College London, London, United Kingdom;"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7266-0890","authenticated-orcid":false,"given":"Karen","family":"Keeshan","sequence":"additional","affiliation":[{"name":"Paul O\u2019Gorman Leukaemia Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, United Kingdom;"}]},{"given":"Salvatore","family":"Santamaria","sequence":"additional","affiliation":[{"name":"The Francis Crick Institute, London, United Kingdom;"}]},{"given":"Edwin","family":"Hawkins","sequence":"additional","affiliation":[{"name":"The Walter and Eliza Hall Institute of Medical Research, University of Melbourne, Parkville, VIC, Australia;"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7198-5965","authenticated-orcid":false,"given":"Brunangelo","family":"Falini","sequence":"additional","affiliation":[{"name":"Institute of Haematology, Centro di Ricerca Emato-Oncologica (CREO), University of Perugia, Perugia, Italy;"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4724-9327","authenticated-orcid":false,"given":"Andrea","family":"Marra","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, Sir Alexander Fleming Building, Imperial College London, London, United Kingdom;"},{"name":"Institute of Haematology, Centro di Ricerca Emato-Oncologica (CREO), University of Perugia, Perugia, Italy;"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3476-0211","authenticated-orcid":false,"given":"Delfim","family":"Duarte","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, Sir Alexander Fleming Building, Imperial College London, London, United Kingdom;"},{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S) Universidade do Porto, Porto, Portugal;"},{"name":"Department of Onco-Hematology, Instituto Portugu\u00eas de Oncologia (IPO), Porto, Portugal; and"},{"name":"Department of Biomedicine, Unit of Biochemistry, Faculdade de Medicina da Universidade do Porto, Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4363-9050","authenticated-orcid":false,"given":"Chiu Fan","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, Imperial College London, London, United Kingdom;"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8229-1715","authenticated-orcid":false,"given":"Edward","family":"Roberts","sequence":"additional","affiliation":[{"name":"Beatson Institute for Cancer Research, Glasgow, United Kingdom;"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1163-4207","authenticated-orcid":false,"given":"Cristina","family":"Lo Celso","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, Sir Alexander Fleming Building, Imperial College London, London, United Kingdom;"},{"name":"The Francis Crick Institute, London, United Kingdom;"},{"name":"Centre for Haematology, Department of Immunology and Inflammation, Imperial College London, London, United Kingdom;"}]}],"member":"234","published-online":{"date-parts":[[2022,5,20]]},"reference":[{"issue":"12","key":"2022052015251285900_B1","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1056\/NEJMra1406184","article-title":"Acute myeloid 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reads","volume":"47","author":"Liao","year":"2019","journal-title":"Nucleic Acids Res."},{"issue":"1","key":"2022052015251285900_B31","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1038\/s41556-019-0439-6","article-title":"Combined single-cell and spatial transcriptomics reveal the molecular, cellular and spatial bone marrow niche organization","volume":"22","author":"Baccin","year":"2020","journal-title":"Nat Cell Biol."},{"issue":"5","key":"2022052015251285900_B32","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1038\/nbt.4096","article-title":"Integrating single-cell transcriptomic data across different conditions, technologies, and species","volume":"36","author":"Butler","year":"2018","journal-title":"Nat Biotechnol."},{"issue":"7","key":"2022052015251285900_B33","doi-asserted-by":"crossref","first-page":"1915","DOI":"10.1016\/j.cell.2019.04.040","article-title":"A cellular taxonomy of the bone marrow stroma in homeostasis and leukemia","volume":"177","author":"Baryawno","year":"2019","journal-title":"Cell."},{"issue":"7728","key":"2022052015251285900_B34","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1038\/s41586-018-0623-z","article-title":"Functional genomic landscape of acute myeloid leukaemia","volume":"562","author":"Tyner","year":"2018","journal-title":"Nature."},{"issue":"Pt 3","key":"2022052015251285900_B35","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1242\/jcs.006064","article-title":"Extracellular matrix dynamics in development and regenerative medicine","volume":"121","author":"Daley","year":"2008","journal-title":"J Cell Sci."},{"issue":"4","key":"2022052015251285900_B36","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1083\/jcb.201102147","article-title":"The extracellular matrix: a dynamic niche in cancer progression","volume":"196","author":"Lu","year":"2012","journal-title":"J Cell Biol."},{"issue":"1","key":"2022052015251285900_B37","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1186\/s12885-019-5768-0","article-title":"A pan-cancer perspective of matrix metalloproteases (MMP) gene expression profile and their diagnostic\/prognostic potential","volume":"19","author":"Gobin","year":"2019","journal-title":"BMC Cancer."},{"issue":"4","key":"2022052015251285900_B38","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1046\/j.1365-2141.2002.03510.x","article-title":"Marrow matrix metalloproteinases (MMPs) and tissue inhibitors of MMP in acute leukaemia: potential role of MMP-9 as a surrogate marker to monitor leukaemic status in patients with acute myelogenous leukaemia","volume":"117","author":"Lin","year":"2002","journal-title":"Br J Haematol."},{"issue":"2","key":"2022052015251285900_B39","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1111\/j.1365-2141.2004.04877.x","article-title":"The role of matrix metalloproteinase 9 in the 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and PDGF-BB expression","volume":"30","author":"Woenne","year":"2010","journal-title":"Anticancer Res."},{"issue":"7599","key":"2022052015251285900_B43","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1038\/nature17624","article-title":"Distinct bone marrow blood vessels differentially regulate haematopoiesis","volume":"532","author":"Itkin","year":"2016","journal-title":"Nature."},{"issue":"2","key":"2022052015251285900_B44","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1111\/imcb.12216","article-title":"Defining the in\u00a0vivo characteristics of acute myeloid leukemia cells behavior by intravital imaging","volume":"97","author":"Duarte","year":"2019","journal-title":"Immunol Cell Biol."},{"issue":"6","key":"2022052015251285900_B45","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1016\/j.cell.2007.05.014","article-title":"A microenvironment-induced myeloproliferative syndrome caused by retinoic acid receptor gamma deficiency","volume":"129","author":"Walkley","year":"2007","journal-title":"Cell."},{"issue":"7290","key":"2022052015251285900_B46","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1038\/nature08851","article-title":"Bone progenitor dysfunction induces myelodysplasia and secondary leukaemia","volume":"464","author":"Raaijmakers","year":"2010","journal-title":"Nature."},{"issue":"11","key":"2022052015251285900_B47","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.1038\/nm.3364","article-title":"Differential regulation of myeloid leukemias by the bone marrow microenvironment","volume":"19","author":"Krause","year":"2013","journal-title":"Nat Med."},{"issue":"3","key":"2022052015251285900_B48","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/j.stem.2015.02.014","article-title":"Normal and leukemic stem cell niches: insights and therapeutic opportunities","volume":"16","author":"Schepers","year":"2015","journal-title":"Cell Stem 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