KDM3B shows tumor-suppressive activity and transcriptionally regulates HOXA1 through retinoic acid response elements in acute myeloid leukemia

Leuk Lymphoma. 2018 Jan;59(1):204-213. doi: 10.1080/10428194.2017.1324156. Epub 2017 May 25.


KDM3B reportedly shows both tumor-suppressive and tumor-promoting activities in leukemia. The function of KDM3B is likely cell-type dependent and its seeming functional discordance may reflect its phenotypic dependence on downstream targets. Here, we first showed the underexpression of KDM3B in acute myeloid leukemia (AML) patients and AML cell lines with MLL-AF6/9 or PML-RARA translocations. Overexpression of KDM3B repressed colony formation of AML cell line with 5q deletion. We then performed global microarray profiling to identify potential downstream targets of KDM3B, notably HOXA1, which was verified by real time PCR and Western blotting. We further showed KDM3B binding at retinoic acid response elements (RARE) but not at the promoter region of HOXA1 gene. KDM3B knockdown resulted in increased mono-methylation but decreased di-methylation of H3K9 at RARE while eschewing the promoter region of HOXA1. Collectively, we found that KDM3B exhibits potential tumor-suppressive activity and transcriptionally modulates HOXA1 expression via RARE in AML.

Keywords: Histone demethylation; MLL-rearrangement; PML-RARA translocations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Gene Expression Regulation, Leukemic* / drug effects
  • Histones / metabolism
  • Homeodomain Proteins / genetics*
  • Humans
  • Jumonji Domain-Containing Histone Demethylases / genetics
  • Jumonji Domain-Containing Histone Demethylases / metabolism*
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / metabolism*
  • Methylation
  • Oncogene Proteins, Fusion / genetics
  • Oncogene Proteins, Fusion / metabolism
  • Promoter Regions, Genetic
  • Response Elements*
  • Transcription Factors / genetics*
  • Translocation, Genetic*
  • Tretinoin / pharmacology


  • Histones
  • Homeodomain Proteins
  • Oncogene Proteins, Fusion
  • Transcription Factors
  • homeobox A1 protein
  • promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein
  • Tretinoin
  • Jumonji Domain-Containing Histone Demethylases
  • KDM3B protein, human