Gene Technology Center


2019年 9月26日〜28日(京都)
タイトル; RUNX3 over-expression impedes RUNX1 function and promotes the development of myelodysplastic syndrome.
発表者;横溝 貴子氏
(熊本大学 国際先端医学研究機構 指田研究室)
RUNX3 functions as either tumor suppressor or oncogene, however, it remains unknown how RUNX3 promotes the formation of myeloid malignancies including myelodysplastic syndromes (MDS). We found that RUNX3 expression was increased in a subset of patients of MDS. To determine how RUNX3 promotes the formation of MDS, we generated a hematopoietic-specific Tet2 null and RUNX3 overexpressing (Tet2KO-RUNX3) mouse model. Tet2KO-RUNX3 mice significantly developed MDS characterized with pancytopenia and dysplastic cells compared to single mutant mice. To understand the molecular mechanism, we performed RNA- and ChIP-sequencing analyses in LSK or LK cells from Tet2KO-RUNX3 MDS mice and found significantly suppressed expression levels of canonical Runx1 target genes resulted from suppressed protein level of Runx1 and competed Runx1 binding region with Runx3. In addition, enhanced expression of c-myc target genes were found in Tet2KO-RUNX3 HSPCs which was sensitive to Myc inhibitor leading to impaired cell proliferation. Thus, RUNX3 overexpression suppresses function of Runx1 and activates Myc oncogenic pathway, which cooperatively promotes the development of MDS in TET2 deficient cells.


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