title: KDM2b/JHDM1b, an H3K36me2-specific demethylase, is required for initiation and maintenance of acute myeloid leukemia.
abstract: The histone H3 lysine 36 dimethyl-specific demethylase KDM2b/JHDM1b, which is highly expressed in various human leukemias, was previously found to be important in regulating cell proliferation and cellular senescence. However, its functions in leukemia development and maintenance are unclear. Here, we demonstrate that ectopic expression of Kdm2b/Jhdm1b is sufficient to transform hematopoietic progenitors. Conversely, depletion of Kdm2b/Jhdm1b in hematopoietic progenitors significantly impairs Hoxa9/Meis1-induced leukemic transformation. In leukemic stem cells, knockdown of Kdm2b/Jhdm1b impairs their self-renewing capability in vitro and in vivo. The functions of Kdm2b/Jhdm1b are mediated by its silencing of p15(Ink4b) expression through active demethylation of histone H3 lysine 36 dimethyl. Thus, our study suggests that Kdm2b/Jhdm1b functions as an oncogene and plays a critical role in leukemia development and maintenance.
authors.affiliation: Howard Hughes Medical Institute, and Department of Biochemistry and Biophysics, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, NC 27599, USA.
authors.forename: Jin
authors.initials: J
authors.lastname: He
authors.forename: Anh Tram
authors.initials: AT
authors.lastname: Nguyen
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D018450:Disease Progression; D004622:Embryo, Mammalian; D044783:F-Box Proteins / Q000235:genetics / Q000502:physiology*; D015973:Gene Expression Regulation, Leukemic; D006657:Histones / Q000378:metabolism; D006801:Humans; D056484:Jumonji Domain-Containing Histone Demethylases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology; D013379:Substrate Specificity / Q000235:genetics; D014162:Transfection
chemical_list: D044783:F-Box Proteins; D006657:Histones; D056484:Jumonji Domain-Containing Histone Demethylases; C524747:Kdm2b protein, mouse