Data from Overexpression of RUNX3 Represses RUNX1 to Drive Transformation of Myelodysplastic Syndrome

• DOI: 10.1158/0008-5472.c.6511596.v1
• Publication Date: 2023-03-31T21:52:32Z
• Authors: Takako Yokomizo-N...; Sho Kubota; Jie Bai; Ai Hamashima; Mariko Morii; Yuqi Sun; Seiichiro Katagiri; Mihoko Iimori; Akinori Kanai; Daiki Tanaka; Motohiko Oshima; Yuka Harada; Kazuma Ohyashiki; Atsushi Iwama; Hironori Harada; Motomi Osato; Goro Sashida
• Keywords: RUNX1; CEBPA

<div>Abstract<p>RUNX3, a RUNX family transcription factor, regulates normal hematopoiesis and functions as tumor suppressor in various tumors humans mice. However, emerging studies have documented increased expression of RUNX3 hematopoietic stem/progenitor cells (HSPC) subset patients with myelodysplastic syndrome (MDS) showing worse outcome, suggesting an oncogenic function for the pathogenesis hematologic malignancies. To elucidate MDS <i>in vivo</i>, we generated <i>RUNX3</i>-expressing, <i>Tet2</i>-deficient mouse model pancytopenia dysplastic blood characteristic patients. RUNX3-expressing markedly suppressed levels Runx1, critical regulator hemaotpoiesis malignant cells, well its target genes, which included crucial suppressors such <i>Cebpa</i> <i>Csf1r</i>. bound these genes remodeled their Runx1-binding regions Tet2-deficient cells. Overexpression inhibited transcriptional Runx1 compromised to facilitate development absence Tet2, indicating that <i>RUNX3</i> is oncogene. Furthermore, overexpression activated Myc rendered sensitive inhibition Myc-Max heterodimerization. Collectively, results reveal mechanism by exerts effects on cellular program stem drive transformation MDS.</p>Significance:<p>This study defines factor driving syndrome, highlighting potential therapeutic intervention.</p></div>