페이지 정보작성자 Science (35.♡.154.111) 댓글 0건 조회 48회 작성일 2021-10-12 17:35
KBM (Korean Biological Research Group in Michigan)은 의학, 약학, 생물학 관련 연구를 수행하는 연구자들의 모임입니다 [홈페이지].
매달 셋째 주 화요일 저녁 6시에 온라인으로 학술 세미나 및 네트워킹을 진행하고 있으며, 현재 UofM 뿐만 아니라 다른 학교와의 교류도 도모하고 있습니다.
이번 세미나는 10월 19일(화) 오후 6시 Department of Pathology 소속으로 계시는 김은기 박사님께서 “Combinatorial treatment with menin and FLT3 inhibitors induces complete remission in AML models with activating FLT3 mutations” 란 주제로 발표해 주십니다.
The interaction between menin and the mixed lineage leukemia (MLL1) protein plays an important role in aggressive acute leukemia with translocations of the MLL1 (KMT2A) gene and with mutations in the nucleophosmin (NPM1) gene. We and others have recently shown that small-molecule inhibitors of the menin-MLL1 interaction can effectively block leukemia progression in these leukemia subtypes. Activating mutations in FLT3 kinase are found in a substantial fraction of AML patients, leading to poor clinical outcomes. Because mutations in FLT3 often co-occur with MLL1 translocations and NPM1 mutations, we hypothesized that the antileukemic activity of menin inhibitors may synergize with FLT3 inhibitors, paving the way for clinical translation of such drug combinations in leukemia. In this study, we discovered that only the combination of menin and FLT3 inhibitors could cure mice in aggressive leukemia models harboring activating FLT3 mutations in addition to MLL1 translocations or NPM1 mutations. Mechanistically, this combination induced stronger downregulation of MEIS1 and HOXA cluster genes and demonstrated a more pronounced effect on MYC, stemness, and differentiation pathways over single agents, concurring with a recent report. Importantly, we found that the combination of potent menin and FLT3 inhibitors was particularly effective in vivo, leading to complete and long-lasting remission of leukemia in mice. Our findings can be directly translated to initiate clinical trials with this combination in AML patients.
l 관련논문 링크
많은 관심과 참여 부탁 드립니다.
장소: Biological Sciences Building (BSB), Room 5150
주소: 1105 N University Ave, Ann Arbor, MI 48109
시간: 10월 19일(화) 오후 6시
Zoom link: https://umich.zoom.us/j/94959288931
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