{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:33:33Z","timestamp":1792787613889,"version":"4.5.0"},"reference-count":63,"publisher":"American Society for Clinical Investigation","issue":"19","license":[{"start":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:00:00Z","timestamp":1791417600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NHLBI","award":["R01HL124015"],"award-info":[{"award-number":["R01HL124015"]}],"id":[{"id":"https:\/\/ror.org\/012pb6c26","id-type":"ROR","asserted-by":"crossref"}]},{"name":"NHLBI","award":["R21AI193881"],"award-info":[{"award-number":["R21AI193881"]}],"id":[{"id":"https:\/\/ror.org\/012pb6c26","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,8]]},"abstract":"<jats:p>\n                    Acute myeloid leukemia (AML) is the most common adult leukemia diagnosis. Bone marrow (BM) niche significantly influences the initiation and progression of AML. However, our knowledge about the effect of leukemic niche on leukemia stem cells (LSC) and leukemogenesis is limited. In this study, we identified an extrinsic-regulatory function of latexin (\n                    <jats:italic>Lxn<\/jats:italic>\n                    ) in leukemogenesis. Using a MLL-AF9\u2013induced AML mouse model in WT and\n                    <jats:italic>Lxn<\/jats:italic>\n                    -KO (\n                    <jats:italic>\n                      Lxn\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    ) recipient mice, we found that\n                    <jats:italic>Lxn<\/jats:italic>\n                    deletion in the BM niche enhanced the survival of AML mice by suppressing LSCs and reducing blood blasts. Single-cell RNA-seq of stromal cells and cell communication analysis uncovered downregulation of the leukemia inhibitory factor receptor (LIFR) signaling pathway in the\n                    <jats:italic>\n                      Lxn\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    niche, particularly within mesenchymal stromal cells (MSCs). Mechanistically, reduced LIFR level in Lxn\n                    <jats:italic>\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    MSCs upregulated\n                    <jats:italic>Cxcl9<\/jats:italic>\n                    expression, leading to increased recruitment of CD8 T cells and enhanced cytotoxicity against leukemic cells. Combination of\n                    <jats:italic>Lxn<\/jats:italic>\n                    niche deletion and immune checkpoint inhibitor PD-1 further prolonged survival. The findings have important clinical implications, suggesting that\n                    <jats:italic>Lxn<\/jats:italic>\n                    inhibition could improve the efficacy of AML therapies by targeting the leukemia niche and enhancing immune surveillance.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.199771","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T18:00:57Z","timestamp":1791396057000},"source":"Crossref","is-referenced-by-count":0,"title":["Latexin deletion in the bone marrow niche suppresses leukemia via LIFR downregulation and immune activation"],"prefix":"10.1172","volume":"11","author":[{"given":"Cuiping","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Toxicology and Cancer Biology, University of Kentucky, Lexington, Kentucky, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Yao","sequence":"additional","affiliation":[{"name":"Lindsley F. Kimball Research Institute, New York Blood Center, Rye, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3779-9592","authenticated-orcid":true,"given":"Pinpin","family":"Sui","sequence":"additional","affiliation":[{"name":"Department of Cell Systems & Anatomy, University of Texas Health at San Antonio, San Antonio, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liming","family":"Hou","sequence":"additional","affiliation":[{"name":"Department of Toxicology and Cancer Biology, University of Kentucky, Lexington, Kentucky, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bowen","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Pharmacodynamics, College of Pharmacy, University of Florida, Gainesville, Florida, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larry L.","family":"Luchsinger","sequence":"additional","affiliation":[{"name":"Department of Toxicology and Cancer Biology, University of Kentucky, Lexington, Kentucky, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Cell Systems & Anatomy, University of Texas Health at San Antonio, San Antonio, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng","family":"Tong","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, University of Kentucky, Lexington, Kentucky, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youwen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Center for Computational and Integrative Biology, Rutgers University-Camden, Camden, New Jersey, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bojing","family":"Shao","sequence":"additional","affiliation":[{"name":"Department of Toxicology and Cancer Biology, University of Kentucky, Lexington, Kentucky, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2512-9199","authenticated-orcid":true,"given":"Hong","family":"Qian","sequence":"additional","affiliation":[{"name":"Karolinska Institute, Flemingsberg Campus, Huddinge, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Zheng","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Penn State University College of Medicine, Hershey, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Toxicology and Cancer Biology, University of Kentucky, Lexington, Kentucky, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng-Chun","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Cell Systems & Anatomy, University of Texas Health at San Antonio, San Antonio, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Toxicology and Cancer Biology, University of Kentucky, Lexington, Kentucky, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2026,10,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1516192"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-018-0027-x"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-019-0230-9"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2253"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2006.08.020"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-020-0245-2"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2024.1365330"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-41994-0"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2023.106943"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-75429-7"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1158\/2643-3230.BCD-23-0125"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1158\/2643-3230.BCD-23-0043"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2021012299"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.04.040"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2015.08.006"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2017013870"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.90036"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2017.11.006"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-023-01282-2"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2021011510"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1038\/nature08851"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2005.02.009"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.05.014"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.03.055"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-03-148999"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1038\/nature12883"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1038\/nature20131"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2017013599"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-03-343467"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.scr.2015.01.004"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1038\/ng1938"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1038\/ng0207-141"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1038\/nrg1206"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2022.282028"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2023.112274"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2018.207092"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1097\/MOH.0000000000000428"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2017.02.009"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2014.443"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0044979"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2008.01.032"},{"key":"B42","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1007\/7651_2020_298","article-title":"Interactions of hematopoietic stem cells with bone marrow niche","volume":"2346","author":"Zhao","year":"2021","journal-title":"Methods Mol Biol"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2013.06.009"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2013.10.010"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2021.05.018"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2020.107158"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1007\/s11914-023-00837-z"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1172\/JCI182125"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1016\/j.gendis.2021.04.003"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.3390\/biom12020217"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.693724"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-10369-9"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1080\/14737159.2017.1381560"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2026.1608433"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2020.06.013"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1104-8"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1111\/j.1601-6343.2009.01447.x"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2007.10.015"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.05.031"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1016\/j.cels.2018.11.005"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-018-0121-4"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-12-821413"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-21246-9"}],"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/insight.jci.org\/articles\/view\/199771\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T18:01:01Z","timestamp":1791396061000},"score":1,"resource":{"primary":{"URL":"https:\/\/insight.jci.org\/articles\/view\/199771"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,8]]},"references-count":63,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2026,8,18]]},"published-print":{"date-parts":[[2026,10,8]]}},"alternative-id":["10.1172\/jci.insight.199771"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.199771","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,8]]},"article-number":"e199771"}}