{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T23:06:43Z","timestamp":1779232003885,"version":"3.51.4"},"reference-count":73,"publisher":"American Society for Clinical Investigation","issue":"24","license":[{"start":{"date-parts":[[2024,12,16]],"date-time":"2024-12-16T00:00:00Z","timestamp":1734307200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Florida Department of Health Live Like Bella Pediatric Cancer Research Initiative.","award":["21L02"],"award-info":[{"award-number":["21L02"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,12,16]]},"abstract":"<jats:p>\n                    Ecotropic viral integration site 1 (EVI1\/MECOM) is frequently upregulated in myeloid malignancies. Here, we present an Evi1-transgenic mouse model with inducible expression in hematopoietic stem\/progenitor cells (HSPCs). Upon induction of\n                    <jats:italic>Evi1<\/jats:italic>\n                    expression, mice displayed anemia, thrombocytopenia, lymphopenia, and erythroid and megakaryocyte dysplasia with a significant expansion of committed myeloid progenitor cells, resembling human myelodysplastic syndrome\/myeloproliferative neoplasm\u2013like (MDS\/MPN\u2013like) disease. Evi1 overexpression prompted HSPCs to exit quiescence and accelerated their proliferation, leading to expansion of committed myeloid progenitors while inhibiting lymphopoiesis. Analysis of global gene expression and Evi1 binding site profiling in HSPCs revealed that Evi1 directly upregulated lysine demethylase 6b (Kdm6b). Subsequently, Kdm6b-mediated H3K27me3 demethylation resulted in activation of various genes, including\n                    <jats:italic>Laptm4b<\/jats:italic>\n                    . Interestingly,\n                    <jats:italic>KDM6B<\/jats:italic>\n                    and\n                    <jats:italic>LAPTM4B<\/jats:italic>\n                    are positively correlated with\n                    <jats:italic>EVI1<\/jats:italic>\n                    expression in patients with MDS. The EVI1\/KDM6B\/H3K27me3\/LAPTM4B signaling pathway was also identified in EVI1\n                    <jats:sup>hi<\/jats:sup>\n                    human leukemia cell lines. We found that hyperactivation of the LAPTM4B-driven mTOR pathway was crucial for the growth of EVI1\n                    <jats:sup>hi<\/jats:sup>\n                    leukemia cells. Knockdown of Laptm4b partially rescued Evi1-induced abnormal hematopoiesis in vivo. Thus, our study establishes a mouse model to investigate EVI1\n                    <jats:sup>hi<\/jats:sup>\n                    myeloid malignancies, demonstrating the significance of the EVI1-mediated KDM6B\/H3K27me3\/LAPTM4B signaling axis in their maintenance.\n                  <\/jats:p>","DOI":"10.1172\/jci173403","type":"journal-article","created":{"date-parts":[[2024,12,15]],"date-time":"2024-12-15T14:00:43Z","timestamp":1734271243000},"source":"Crossref","is-referenced-by-count":2,"title":["Evi1 governs Kdm6b-mediated histone demethylation to regulate the Laptm4b-driven mTOR pathway in hematopoietic progenitor cells"],"prefix":"10.1172","volume":"134","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9514-9937","authenticated-orcid":true,"given":"Qiong","family":"Wu","sequence":"first","affiliation":[{"name":"Zhejiang Provincial Key Laboratory of Medical Genetics, Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China."},{"name":"Department of Medicine and Department of Biochemistry and Molecular Biology, UF Health Cancer Center, University of Florida, Gainesville, Florida, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2161-3394","authenticated-orcid":true,"given":"Chunjie","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Medicine and Department of Biochemistry and Molecular Biology, UF Health Cancer Center, University of Florida, Gainesville, Florida, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9010-9461","authenticated-orcid":true,"given":"Fang","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Medicine and Department of Biochemistry and Molecular Biology, UF Health Cancer Center, University of Florida, Gainesville, Florida, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yiran","family":"Guo","sequence":"additional","affiliation":[{"name":"Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9424-123X","authenticated-orcid":true,"given":"Yue","family":"Sheng","sequence":"additional","affiliation":[{"name":"Department of Medicine and Department of Biochemistry and Molecular Biology, UF Health Cancer Center, University of Florida, Gainesville, Florida, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liping","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pathology at Geisinger Medical Center, Danville, Pennsylvania, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yafang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Medicine and Department of Biochemistry and Molecular Biology, UF Health Cancer Center, University of Florida, Gainesville, Florida, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yutao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Medicine and Department of Biochemistry and Molecular Biology, UF Health Cancer Center, University of Florida, Gainesville, Florida, USA."},{"name":"Department of Biostatistics, University of Florida, Gainesville, Florida, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chao","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jue","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medicine and Department of Biochemistry and Molecular Biology, UF Health Cancer Center, University of Florida, Gainesville, Florida, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tong-chuan","family":"He","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery and Rehabilitation Medicine, University of Chicago, Chicago, Illinois, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Virginia, Charlottesville, Virginia, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongyu","family":"Ni","sequence":"additional","affiliation":[{"name":"Department of Pathology, Cedars-Sinai Medical Center, Los Angeles, California, 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