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MicroRNA-125b Accelerates and Promotes PML-RARa-driven Murine Acute Promyelocytic Leukemia

摘要Objective Most acute promyelocytic leukemia cases are characterized by the PML-RARa fusion oncogene and low white cell counts in peripheral blood. Methods Based on the frequent overexpression of miR-125-family miRNAs in acute promyelocytic leukemia, we examined the consequence of this phenomenon by using an inducible mouse model overexpressing human miR-125b. Results MiR-125b expression significantly accelerates PML-RARa-induced leukemogenesis, with the resultant induced leukemia being partially dependent on continued miR-125b overexpression. Interestingly, miR-125b expression led to low peripheral white cell counts to bone marrow blast percentage ratio, confirming the clinical observation in acute promyelocytic leukemia patients. Conclusion This study suggests that dysregulated miR-125b expression is actively involved in disease progression and pathophysiology of acute promyelocytic leukemia, indicating that targeting miR-125b may represent a new therapeutic option for acute promyelocytic leukemia.

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作者 GUO Bo [1] QIN Ran [2] CHEN Ji Jun [3] PAN Wen [3] LU Xue Chun [2] 学术成果认领
作者单位 Department of Hematology,The Second Medical Centre&National Clinical Research Center for Geriatric Diseases,Chinese PLA General Hospital,Beijing 100853,China;Department of Genetics,Yale University School of Medicine,New Haven,Connecticut 06510,USA;Yale Stem Cell Center,Yale Cancer Center,New Haven,CT,06520,USA [1] Department of Hematology,The Second Medical Centre&National Clinical Research Center for Geriatric Diseases,Chinese PLA General Hospital,Beijing 100853,China [2] Department of Genetics,Yale University School of Medicine,New Haven,Connecticut 06510,USA;Yale Stem Cell Center,Yale Cancer Center,New Haven,CT,06520,USA [3]
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DOI 10.3967/bes2022.067
发布时间 2022-07-06(万方平台首次上网日期,不代表论文的发表时间)
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