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Here we show CD99, a protein upregulated in leukemia stem cells (LSCs) in acute myeloid leukemia (AML), is required for the self-renewal of proliferating HSCs and LSCs. We found that loss of CD99 in HSCs and LSCs leads to increased protein synthesis, and that their self-renewal capacity can be restored by translation inhibition. These data demonstrate a functional role for CD99 in constraining protein synthesis, which may promote the clonal expansion of HSCs and LSCs that leads to AML. Furthermore, these studies demonstrate that similar to HSCs, LSCs depend on maintenance of tightly regulated protein synthesis rates.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1182\/blood.2024026271","type":"journal-article","created":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T18:17:48Z","timestamp":1753294668000},"page":"1914-1928","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":3,"title":["CD99 promotes self-renewal in hematopoietic stem cells and leukemia stem cells by regulating protein synthesis"],"prefix":"10.1182","volume":"146","author":[{"given":"Yuanyuan","family":"Ji","sequence":"first","affiliation":[{"name":"1Division of Hematology\/Oncology, Department of Internal Medicine, Children\u2019s Medical Center Research Institute, The University of Texas Southwestern Medical Center, Dallas, TX"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Huang","sequence":"additional","affiliation":[{"name":"1Division of Hematology\/Oncology, Department of Internal Medicine, Children\u2019s Medical Center Research Institute, The University of Texas Southwestern Medical Center, Dallas, TX"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-1707-4951","authenticated-orcid":false,"given":"Toby","family":"Thomas","sequence":"additional","affiliation":[{"name":"1Division of Hematology\/Oncology, Department of Internal Medicine, Children\u2019s Medical Center Research Institute, The University of Texas Southwestern Medical Center, Dallas, TX"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eda","family":"Gozel Kapti","sequence":"additional","affiliation":[{"name":"1Division of Hematology\/Oncology, Department of Internal Medicine, Children\u2019s Medical Center Research Institute, The University of Texas Southwestern Medical Center, Dallas, TX"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reiko","family":"Tachibana","sequence":"additional","affiliation":[{"name":"1Division of Hematology\/Oncology, Department of Internal Medicine, Children\u2019s Medical Center Research Institute, The University of Texas Southwestern Medical Center, Dallas, TX"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacob","family":"Lark","sequence":"additional","affiliation":[{"name":"1Division of Hematology\/Oncology, Department of Internal Medicine, Children\u2019s Medical Center Research Institute, The University of Texas Southwestern Medical Center, Dallas, TX"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iryna","family":"Berezniuk","sequence":"additional","affiliation":[{"name":"2Department of Pathology, New York University Grossman School of Medicine, New York, NY"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liang","family":"Guo","sequence":"additional","affiliation":[{"name":"2Department of Pathology, New York University Grossman School of Medicine, New York, NY"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2352-2760","authenticated-orcid":false,"given":"Mohamed A. 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