Lineage-specific RUNX2 super-enhancer activates MYC and promotes the development of blastic plasmacytoid dendritic cell neoplasm

Nat Commun. 2019 Apr 10;10(1):1653. doi: 10.1038/s41467-019-09710-z.


Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive subtype of acute leukemia, the cell of origin of which is considered to be precursors of plasmacytoid dendritic cells (pDCs). Since translocation (6;8)(p21;q24) is a recurrent anomaly for BPDCN, we demonstrate that a pDC-specific super-enhancer of RUNX2 is associated with the MYC promoter due to t(6;8). RUNX2 ensures the expression of pDC-signature genes in leukemic cells, but also confers survival and proliferative properties in BPDCN cells. Furthermore, the pDC-specific RUNX2 super-enhancer is hijacked to activate MYC in addition to RUNX2 expression, thereby promoting the proliferation of BPDCN. We also demonstrate that the transduction of MYC and RUNX2 is sufficient to initiate the transformation of BPDCN in mice lacking Tet2 and Tp53, providing a model that accurately recapitulates the aggressive human disease and gives an insight into the molecular mechanisms underlying the pathogenesis of BPDCN.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Proliferation / genetics
  • Chromosomes, Human, Pair 6 / genetics
  • Chromosomes, Human, Pair 8 / genetics
  • Core Binding Factor Alpha 1 Subunit / genetics*
  • Core Binding Factor Alpha 1 Subunit / metabolism
  • DNA-Binding Proteins / genetics
  • Dendritic Cells / pathology*
  • Dioxygenases
  • Enhancer Elements, Genetic / genetics
  • Hematopoietic Stem Cell Transplantation
  • Hematopoietic Stem Cells
  • Humans
  • Jurkat Cells
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neoplasms, Experimental / genetics
  • Neoplasms, Experimental / pathology
  • Promoter Regions, Genetic / genetics
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins c-myc / genetics*
  • Proto-Oncogene Proteins c-myc / metabolism
  • Translocation, Genetic / genetics
  • Whole-Body Irradiation


  • Core Binding Factor Alpha 1 Subunit
  • DNA-Binding Proteins
  • MYC protein, human
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-myc
  • RUNX2 protein, human
  • Dioxygenases
  • Tet2 protein, mouse