title: Upregulation of miR-99a is associated with poor prognosis of acute myeloid leukemia and promotes myeloid leukemia cell expansion.
abstract: Leukemia stem cells (LSCs) can resist available treatments that results in disease progression and/or relapse. To dissect the microRNA (miRNA) expression signature of relapse in acute myeloid leukemia (AML), miRNA array analysis was performed using enriched LSCs from paired bone marrow samples of an AML patient at different disease stages. We identified that miR-99a was significantly upregulated in the LSCs obtained at relapse compared to the LSCs collected at the time of initial diagnosis. We also found that miR-99a was upregulated in LSCs compared to non-LSCs in a larger cohort of AML patients, and higher expression levels of miR-99a were significantly correlated with worse overall survival and event-free survival in these AML patients. Ectopic expression of miR-99a led to increased colony forming ability and expansion in myeloid leukemia cells after exposure to chemotherapeutic drugs in vitro and in vivo, partially due to overcoming of chemotherapeutic agent-mediated cell cycle arrest. Gene profiling and bioinformatic analyses indicated that ectopic expression of miR-99a significantly upregulated genes that are critical for LSC maintenance, cell cycle, and downstream targets of E2F and MYC. This study suggests that miR-99a has a novel role and potential use as a biomarker in myeloid leukemia progression.
authors: State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.
authors: Xiaohui
authors: X
authors: Si
authors: State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.
authors: Xiaoyun
authors: X
authors: Zhang
authors: State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.
authors: Xing
authors: X
authors: Hao
authors: State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.
authors: Yunan
authors: Y
authors: Li
authors: State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.
authors: Zizhen
authors: Z
authors: Chen
authors: State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.
authors: Yahui
authors: Y
authors: Ding
authors: State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.
authors: Hui
authors: H
authors: Shi
authors: State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.
authors: Jie
authors: J
authors: Bai
authors: State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.|Center for Stem Cell Medicine, Chinese Academy of Medical Sciences, Tianjin, China.|Department of Stem Cell & Regenerative Medicine, Peking Union Medical College, Tianjin, China.
authors: Yingdai
authors: Y
authors: Gao
authors: State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.|Center for Stem Cell Medicine, Chinese Academy of Medical Sciences, Tianjin, China.|Department of Stem Cell & Regenerative Medicine, Peking Union Medical College, Tianjin, China.|Collaborative Innovation Center for Cancer Medicine, Tianjin, China.
authors: Tao
authors: T
authors: Cheng
authors: Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA.|Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL, USA.
authors: Feng-Chun
authors: FC
authors: Yang
authors: State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.|Center for Stem Cell Medicine, Chinese Academy of Medical Sciences, Tianjin, China.|Department of Stem Cell & Regenerative Medicine, Peking Union Medical College, Tianjin, China.
authors: Yuan
authors: Y
authors: Zhou
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D064593:Heterografts; D006801:Humans; D020014:K562 Cells; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D015854:Up-Regulation
chemical_list: C561679:MIRN99 microRNA, human; D035683:MicroRNAs
keywords: acute myeloid leukemia; leukemia stem cell; miR-99a; microRNA