title: Post-transcriptional modulation of C/EBPα prompts monocytic differentiation and apoptosis in acute myelomonocytic leukaemia cells.
abstract: CCAAT/enhancer binding protein alpha (C/EBPα) induction induces monocytic differentiation even in acute myeloid leukaemia (AML). In this study, the induction/activation of C/EBPα in myelomonocytic AML was investigated using a combination of all-trans retinoic acid (ATRA) and RAD001 (Everolimus), a mammalian target of rapamycin complex 1 (mTORC1) inhibitor. Combining these agents increased PU.1, C/EBPε and C/EBPα expression, increased the p42/p30 C/EBPα ratio, and decreased C/EBPα phosphorylation at serine 21, and was accompanied by growth inhibition, induction of CD11b expression and apoptosis in AML cell lines. Thus, agents that induce sufficient levels of C/EBPα expression might be useful in treating AML.
authors.affiliation: Department of Paediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Yoshida
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Imamura
authors.forename: Atsushi
authors.initials: A
authors.lastname: Fujiki
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Hirashima
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Miyachi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Inukai
authors.forename: Hajime
authors.initials: H
authors.lastname: Hosoi
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D045744:Cell Line, Tumor; D002648:Child; D002675:Child, Preschool; D000068338:Everolimus; D005260:Female; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D015479:Leukemia, Myelomonocytic, Acute / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D010766:Phosphorylation / Q000187:drug effects; D012323:RNA Processing, Post-Transcriptional / Q000187:drug effects / Q000502:physiology; D020123:Sirolimus / Q000031:analogs & derivatives / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology; D020298:U937 Cells
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; C515848:CEBPA protein, human; D007166:Immunosuppressive Agents; D014212:Tretinoin; D000068338:Everolimus; D020123:Sirolimus