{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T17:01:13Z","timestamp":1780765273945,"version":"3.54.1"},"posted":{"date-parts":[[2026,6,3]]},"group-title":"Cancer Biology","reference-count":38,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"name":"NIH","award":["K01DK131401"],"award-info":[{"award-number":["K01DK131401"]}]},{"name":"NIH","award":["P01CA108671"],"award-info":[{"award-number":["P01CA108671"]}]},{"name":"NIH","award":["R01AG074092"],"award-info":[{"award-number":["R01AG074092"]}]},{"name":"NIH","award":["R01AG071870"],"award-info":[{"award-number":["R01AG071870"]}]},{"name":"NIH","award":["U01AG073148"],"award-info":[{"award-number":["U01AG073148"]}]},{"name":"NIH","award":["U19AG060917"],"award-info":[{"award-number":["U19AG060917"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,6,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  The\n                  <jats:italic>JAK2<\/jats:italic>\n                  <jats:sup>V617F<\/jats:sup>\n                  (JAK2\n                  <jats:sup>VF<\/jats:sup>\n                  ) driver mutation is found in 95% of patients with polycythemia vera (PV), a progressive myeloproliferative neoplasm. Current treatments suppress excessive hematopoiesis but lack specificity for targeting JAK2\n                  <jats:sup>VF<\/jats:sup>\n                  cells, are unable to deplete mutant stem\/progenitor cells and ultimately result in drug resistance. We discovered that the FDA-approved antibiotic, linezolid (LZD), ameliorates the PV phenotype across multiple model systems. LZD suppressed cell proliferation and STAT5 signaling, altered the cell cycle, and increased apoptosis of\n                  <jats:italic>JAK2<\/jats:italic>\n                  <jats:sup>VF<\/jats:sup>\n                  -harboring human erythroleukemia cells, but not in wild-type acute leukemia cells. Computational modelling indicated that LZD interacts specifically with mutant JAK2\n                  <jats:sup>VF<\/jats:sup>\n                  but not with wild-type JAK2 protein. We further showed that, in\n                  <jats:italic>JAK2<\/jats:italic>\n                  <jats:sup>VF<\/jats:sup>\n                  mice that faithfully recapitulate human PV, LZD mitigates disease burden by selectively targeting\n                  <jats:italic>JAK2<\/jats:italic>\n                  <jats:sup>VF<\/jats:sup>\n                  stem cells thereby normalizing spleen size and blood counts. LZD also inhibited hematopoietic colony formation by patient-derived peripheral blood mononuclear cells, with the more primitive progenitors being preferred targets. Importantly, LZD selectively decreased JAK2\n                  <jats:sup>VF+<\/jats:sup>\n                  colony numbers, without impacting wild-type JAK2 colonies. In all, the data provide a firm foundation for evaluating LZD-like molecules as an effective therapy for PV and other myeloproliferative neoplasms.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Key points<\/jats:title>\n                  <jats:list list-type=\"order\">\n                    <jats:list-item>\n                      <jats:p>\n                        Linezolid acts as a JAK2\n                        <jats:sup>V617F<\/jats:sup>\n                        IZselective inhibitor in PV mouse models and PV patient samples while sparing wildIZtype hematopoiesis.\n                      <\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>\n                        Linezolid acts directly on JAK2\n                        <jats:sup>V617F<\/jats:sup>\n                        hematopoietic stem cells.\n                      <\/jats:p>\n                    <\/jats:list-item>\n                  <\/jats:list>\n                <\/jats:sec>","DOI":"10.64898\/2026.05.31.729063","type":"posted-content","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T22:00:14Z","timestamp":1780524014000},"source":"Crossref","is-referenced-by-count":0,"title":["Linezolid Acts as a Selective Inhibitor of the JAK2\n                  <sup>V617F<\/sup>\n                  Mutation"],"prefix":"10.64898","author":[{"given":"Anisa Azatovna","family":"Gumerova","sequence":"first","affiliation":[{"name":"The Mount Sinai Bone Program and Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Schaniel","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Hematology and Medical Oncology, Mount Sinai Tisch Cancer Center, Myeloproliferative Neoplasm Research Consortium, Icahn School of Medicine at Mount Sinai, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zixing","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Icahn School of Medicine at Mount Sinai, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Althea","family":"Agdamag","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Icahn School of Medicine at Mount Sinai, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuhui","family":"Liu","sequence":"additional","affiliation":[{"name":"The Mount Sinai Bone Program and Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA"},{"name":"Department of Emergency Medicine, Icahn School of Medicine at Mount Sinai, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Principi","sequence":"additional","affiliation":[{"name":"University College London School of Pharmacy, London, WC1N 1AX, UK"},{"name":"UCL Centre for Advanced Research Computing, University College London, WC1H 9RN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob","family":"Kazmi","sequence":"additional","affiliation":[{"name":"Donald and Barbara Zucker School of Medicine at Hofstra\/Northwell, Hempstead, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco Fueyo","family":"Gonzalez","sequence":"additional","affiliation":[{"name":"The Mount Sinai Bone Program and Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jihong","family":"Cui","sequence":"additional","affiliation":[{"name":"Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgii","family":"Pevnev","sequence":"additional","affiliation":[{"name":"The Mount Sinai Bone Program and Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caliana","family":"Yang","sequence":"additional","affiliation":[{"name":"The Mount Sinai Bone Program and Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zehra","family":"Tumoglu","sequence":"additional","affiliation":[{"name":"The Mount Sinai Bone Program and Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Gao","sequence":"additional","affiliation":[{"name":"Wisconsin Blood Cancer Research Institute, Department of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA;"},{"name":"UW Carbone Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tony","family":"Yuen","sequence":"additional","affiliation":[{"name":"The Mount Sinai Bone Program and Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yelena","family":"Ginzburg","sequence":"additional","affiliation":[{"name":"The Mount Sinai Bone Program and Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA"},{"name":"Department of Medicine, Division of Hematology and Medical Oncology, Mount Sinai Tisch Cancer Center, Myeloproliferative Neoplasm Research Consortium, Icahn School of Medicine at Mount Sinai, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey","family":"Glassberg","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Icahn School of Medicine at Mount Sinai, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2650-2925","authenticated-orcid":false,"given":"Shozeb","family":"Haider","sequence":"additional","affiliation":[{"name":"The Mount Sinai Bone Program and Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA"},{"name":"University College London School of Pharmacy, London, WC1N 1AX, UK"},{"name":"UCL Centre for Advanced Research Computing, University College London, WC1H 9RN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mone","family":"Zaidi","sequence":"additional","affiliation":[{"name":"The Mount Sinai Bone Program and Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald","family":"Hoffman","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Hematology and Medical Oncology, Mount Sinai Tisch Cancer Center, Myeloproliferative Neoplasm Research Consortium, Icahn School of Medicine at Mount Sinai, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huihui","family":"Li","sequence":"additional","affiliation":[{"name":"The Mount Sinai Bone Program and Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA"},{"name":"Department of Emergency Medicine, Icahn School of Medicine at Mount Sinai, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026060609350415000_2026.05.31.729063v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hoc.2020.12.001"},{"key":"2026060609350415000_2026.05.31.729063v1.2","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2024-0140OC"},{"key":"2026060609350415000_2026.05.31.729063v1.3","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-03-415646"},{"key":"2026060609350415000_2026.05.31.729063v1.4","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-01-402396"},{"key":"2026060609350415000_2026.05.31.729063v1.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2010.05.015"},{"key":"2026060609350415000_2026.05.31.729063v1.6","doi-asserted-by":"publisher","DOI":"10.1128\/spectrum.00032-22"},{"key":"2026060609350415000_2026.05.31.729063v1.7","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.02308-23"},{"key":"2026060609350415000_2026.05.31.729063v1.8","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkg253"},{"key":"2026060609350415000_2026.05.31.729063v1.9","doi-asserted-by":"publisher","DOI":"10.1016\/S0163-4453(09)60009-8"},{"key":"2026060609350415000_2026.05.31.729063v1.10","doi-asserted-by":"publisher","DOI":"10.1086\/340982"},{"key":"2026060609350415000_2026.05.31.729063v1.11","doi-asserted-by":"publisher","DOI":"10.2147\/IDR.S362358"},{"key":"2026060609350415000_2026.05.31.729063v1.12","doi-asserted-by":"publisher","DOI":"10.1177\/0300060518800126"},{"key":"2026060609350415000_2026.05.31.729063v1.13","first-page":"647","article-title":"Linezolid Induced Twice Pure Red Cell Aplasia in a Patient with Central Nervous System Infection after Allogeneic Stem Cell Transplantation","volume":"15","year":"2016","journal-title":"Iran J Pharm Res"},{"key":"2026060609350415000_2026.05.31.729063v1.14","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-3062.2012.00728.x"},{"key":"2026060609350415000_2026.05.31.729063v1.15","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2024.1338902"},{"key":"2026060609350415000_2026.05.31.729063v1.16","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-06-510222"},{"key":"2026060609350415000_2026.05.31.729063v1.17","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb.2348"},{"key":"2026060609350415000_2026.05.31.729063v1.18","unstructured":"18 Schr\u00f6dinger, L. The PyMOL Molecular Graphics System, Version 1.8. (2015)."},{"key":"2026060609350415000_2026.05.31.729063v1.19","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.540150503"},{"key":"2026060609350415000_2026.05.31.729063v1.20","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2022017976"},{"key":"2026060609350415000_2026.05.31.729063v1.21","doi-asserted-by":"publisher","DOI":"10.1038\/7727"},{"key":"2026060609350415000_2026.05.31.729063v1.22","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-09-742387"},{"key":"2026060609350415000_2026.05.31.729063v1.23","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2404081"},{"key":"2026060609350415000_2026.05.31.729063v1.24","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26083727"},{"key":"2026060609350415000_2026.05.31.729063v1.25","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-04-014712"},{"key":"2026060609350415000_2026.05.31.729063v1.26","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-05-432989"},{"key":"2026060609350415000_2026.05.31.729063v1.27","doi-asserted-by":"publisher","DOI":"10.1161\/circresaha.118.313283"},{"key":"2026060609350415000_2026.05.31.729063v1.28","doi-asserted-by":"publisher","DOI":"10.1007\/s00277-023-05284-5"},{"key":"2026060609350415000_2026.05.31.729063v1.29","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-024-01562-5"},{"key":"2026060609350415000_2026.05.31.729063v1.30","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2016.48"},{"key":"2026060609350415000_2026.05.31.729063v1.31","doi-asserted-by":"publisher","DOI":"10.1097\/moh.0000000000000669"},{"key":"2026060609350415000_2026.05.31.729063v1.32","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2021011480"},{"key":"2026060609350415000_2026.05.31.729063v1.33","doi-asserted-by":"publisher","DOI":"10.1016\/j.exphem.2021.06.003"},{"key":"2026060609350415000_2026.05.31.729063v1.34","doi-asserted-by":"crossref","unstructured":"Kimberly Ornell , A. Identification of novel, potent, and selective JAK2V617F inhibitor . ASH Annual Meeting Abstract Abstract number paper No. 4326 (2025).","DOI":"10.1182\/blood-2025-4326"},{"key":"2026060609350415000_2026.05.31.729063v1.35","doi-asserted-by":"crossref","unstructured":"Anil K Padyana , A. B. Discovery of JAK2V617F mutant specific allosteric inhibitors for the treatment of myeloproliferative neoplasms. ASH Annual Meeting Abstract Abstract Number paper No. 1977 (2025).","DOI":"10.1182\/blood-2025-1977"},{"key":"2026060609350415000_2026.05.31.729063v1.36","doi-asserted-by":"publisher","DOI":"10.1021\/bi1014858"},{"key":"2026060609350415000_2026.05.31.729063v1.37","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0011157"},{"key":"2026060609350415000_2026.05.31.729063v1.38","doi-asserted-by":"publisher","DOI":"10.1021\/acsmedchemlett.7b00153"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.05.31.729063","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T16:35:16Z","timestamp":1780763716000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.05.31.729063"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,3]]},"references-count":38,"URL":"https:\/\/doi.org\/10.64898\/2026.05.31.729063","relation":{},"subject":[],"published":{"date-parts":[[2026,6,3]]},"subtype":"preprint"}}