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Stemness properties, including quiescence, self\u2010renewal, and chemoresistance, are maintained through an interplay between leukemia cells and the bone marrow (BM) niche. Here, we demonstrated that DNA damage\u2010inducible transcript 4 (DDIT4) can be induced in a hypoxic BM niche and is required for the quiescence and self\u2010renewal of AML1\u2010ETO9a (AE9a)\u2010transformed leukemia cells\n                    <jats:italic>in vitro<\/jats:italic>\n                    . More importantly, analysis of publicly available transcriptional data from adult acute myeloid leukemia (AML) patients revealed that elevated DDIT4 expression correlates with poor prognosis. Furthermore, DDIT4 knockout markedly suppressed leukemia initiation, quiescence, chemoresistance, and self\u2010renewal of AE9a\u2010transformed leukemia cells\n                    <jats:italic>in vivo<\/jats:italic>\n                    . Mechanistically, DDIT4 upregulates the expression of HOXA gene cluster, and re\u2010expression of\n                    <jats:italic>HOXA6<\/jats:italic>\n                    in DDIT4 knockout AE9a cells can rescue the impaired leukemia initiation. Our findings demonstrate the critical role of DDIT4 in the stemness of AE9a leukemia cells and elucidate its underlying mechanism, suggesting that targeting DDIT4 may represent a promising therapeutic strategy for eliminating LSCs in AML1\u2010ETO leukemia.\n                  <\/jats:p>","DOI":"10.1002\/1878-0261.70090","type":"journal-article","created":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T07:44:08Z","timestamp":1751874248000},"page":"3156-3174","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["The critical role of\n                    <scp>DNA<\/scp>\n                    damage\u2010inducible transcript 4 (\n                    <scp>DDIT4<\/scp>\n                    ) in stemness character of leukemia cells and leukemia initiation"],"prefix":"10.1002","volume":"19","author":[{"given":"Yishuang","family":"Li","sequence":"first","affiliation":[{"name":"State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Tianjin Key Laboratory of Cell Therapy for Blood Diseases, Institute of Hematology &amp; Blood Diseases Hospital Chinese Academy of Medical Sciences &amp; Peking Union Medical College  Tianjin China"},{"name":"Tianjin Institutes of Health Science  China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhijie","family":"Cao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Tianjin Key Laboratory of Cell Therapy for Blood Diseases, Institute of Hematology &amp; Blood Diseases Hospital Chinese Academy of Medical Sciences &amp; Peking Union Medical College  Tianjin China"},{"name":"Tianjin Institutes of Health Science  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Tianjin China"},{"name":"Tianjin Institutes of Health Science  China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenbing","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Tianjin Key Laboratory of Cell Therapy for Blood Diseases, Institute of Hematology &amp; Blood Diseases Hospital Chinese Academy of Medical Sciences &amp; Peking Union Medical College  Tianjin China"},{"name":"Tianjin Institutes of Health Science  China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiayuan","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Tianjin Key Laboratory of Cell Therapy for Blood Diseases, Institute of Hematology &amp; Blood Diseases Hospital Chinese 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Institute of Hematology &amp; Blood Diseases Hospital Chinese Academy of Medical Sciences &amp; Peking Union Medical College  Tianjin China"},{"name":"Tianjin Institutes of Health Science  China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Wei","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Tianjin Key Laboratory of Cell Therapy for Blood Diseases, Institute of Hematology &amp; Blood Diseases Hospital Chinese Academy of Medical Sciences &amp; Peking Union Medical College  Tianjin China"},{"name":"Tianjin Institutes of Health Science  China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shaowei","family":"Qiu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, 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