KDM2b/JHDM1b, an H3K36me2-specific demethylase, is required for initiation and maintenance of acute myeloid leukemia

Blood. 2011 Apr 7;117(14):3869-80. doi: 10.1182/blood-2010-10-312736. Epub 2011 Feb 10.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Transformation, Neoplastic / genetics*
  • Cell Transformation, Neoplastic / metabolism
  • Cell Transformation, Neoplastic / pathology
  • Cells, Cultured
  • Disease Progression
  • Embryo, Mammalian
  • F-Box Proteins / genetics
  • F-Box Proteins / physiology*
  • Gene Expression Regulation, Leukemic
  • Histones / metabolism
  • Humans
  • Jumonji Domain-Containing Histone Demethylases / genetics
  • Jumonji Domain-Containing Histone Demethylases / metabolism
  • Jumonji Domain-Containing Histone Demethylases / physiology*
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / pathology
  • Mice
  • Mice, Inbred C57BL
  • Models, Biological
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology
  • Substrate Specificity / genetics
  • Transfection


  • F-Box Proteins
  • Histones
  • Jumonji Domain-Containing Histone Demethylases
  • Kdm2b protein, mouse