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This acute myeloid leukemia subtype is characterized by the formation of the AML1-ETO fusion gene. However, the AML1-ETO fusion gene alone is not sufficient to drive leukemia development. Additional mutations are required for leukemogenesis. In this study, we aim to investigate whether mutated CCND2 can cooperate with the AML1-ETO fusion gene to drive leukemia initiation and progression.<\/jats:p>\n               <jats:p>In our previous study, the conditional AML1-ETO knock-in mouse model (AML1-ETO mouse), which represented a preleukemia stage as a myeloproliferative neoplasm phenotype, was established. To confirm whether the AML1-ETO and CCND2 mutation can cooperate to drive leukemia, the mice transduction and transplantation model harboring both AML1-ETO and CCND2 genes (both wild-type and mutant) was established. Upon the assessment of the phenotype, biological features, and survival of the mice, only the mice overexpressing AML1-ETO and CCND2 simultaneously eventually progressed to leukemia. Besides, compared to mice overexpressing the AML-ETO gene alone, mTOR and cell cycle\u2013related pathways were significantly enriched in mice harboring both AML1-ETO and CCND2. The selective mTOR inhibitor everolimus can also reduce the leukemia burden and prolong the survival of this group of mice. In conclusion, it was confirmed that the introduction of the CCND2 gene into the AML\/ETO preleukemia mice could trigger the development of leukemia. It was also confirmed that CCND2 overexpression resulted in the upregulation of the mTOR pathway, and inhibiting the pathway might be a therapeutic strategy for this subtype of leukemia.<\/jats:p>","DOI":"10.1093\/jleuko\/qiaf072","type":"journal-article","created":{"date-parts":[[2025,5,22]],"date-time":"2025-05-22T10:39:33Z","timestamp":1747910373000},"source":"Crossref","is-referenced-by-count":5,"title":["AML1-ETO and CCND2 overexpression cooperate to drive acute myeloid leukemia initiation and progression"],"prefix":"10.1093","volume":"117","author":[{"given":"Junli","family":"Mou","sequence":"first","affiliation":[{"name":"State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Tianjin Key Laboratory of Cell Therapy for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College , Tianjin 300020 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