Reference - Detail
| RRC ID | 77031 |
|---|---|
| Author | Kubota S, Tokunaga K, Umezu T, Yokomizo-Nakano T, Sun Y, Oshima M, Tan KT, Yang H, Kanai A, Iwanaga E, Asou N, Maeda T, Nakagata N, Iwama A, Ohyashiki K, Osato M, Sashida G. |
| Title | Lineage-specific RUNX2 super-enhancer activates MYC and promotes the development of blastic plasmacytoid dendritic cell neoplasm. |
| Journal | Nat Commun |
| 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. |
| Volume | 10(1) |
| Pages | 1653 |
| Published | 2019-4-10 |
| DOI | 10.1038/s41467-019-09710-z |
| PII | 10.1038/s41467-019-09710-z |
| PMID | 30971697 |
| PMC | PMC6458132 |
| MeSH | 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 |
| IF | 12.121 |
| Resource | |
| Human and Animal Cells | Jurkat |