RUNX2 super-enhancer promotes the development of blastic plasmacytoid dendritic cell neoplasm

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive acute leukemia, which appears to be originated from the precursor of plasmacytoid dendritic cells (pDCs). Chromosomal translocation t(6;8)(p21;q24) is often seen in BPDCN patients. RUNX2, located on chromosome 6p21, has been shown to regulate the differentiation of pDCs. We found that expression of RUNX2 and C-MYC, an potent oncogene, were significantly up-regulated in BPDCN bone marrow cells in patients as well as a cell line, CAL1, harboring t(6;8)(p21;q24). To detect accuarate translocation sites, we examined whole genome sequencing in CAL1 cells. To find super-enhancer of BPDCN, we examined ChIP-seq analysis with H3K27Ac antibodies in CAL1 cells. Given that RUNX2 appeared to be critical for the development of BPDCN, we examined gene expression profiles of shRNA-directed RUNX2 transduced CAL1 cells compared to the control vector transduced CAL1 cells.