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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-12

AUTHORS

Sho Kubota, Kenji Tokunaga, Tomohiro Umezu, Takako Yokomizo-Nakano, Yuqi Sun, Motohiko Oshima, Kar Ton Tan, Henry Yang, Akinori Kanai, Eisaku Iwanaga, Norio Asou, Takahiro Maeda, Naomi Nakagata, Atsushi Iwama, Kazuma Ohyashiki, Motomi Osato, Goro Sashida

ABSTRACT

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. More... »

PAGES

1653

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41467-019-09710-z

    DOI

    http://dx.doi.org/10.1038/s41467-019-09710-z

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1113355912

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/30971697


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