气候变化领域集成服务门户(CCPortal): Therapeutic targeting of preleukemia cells in a mouse model of NPM1 mutant acute myeloid leukemia

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DOI	10.1126/science.aax5863
	Therapeutic targeting of preleukemia cells in a mouse model of NPM1 mutant acute myeloid leukemia
	Uckelmann H.J.; Kim S.M.; Wong E.M.; Hatton C.; Giovinazzo H.; Gadrey J.Y.; Krivtsov A.V.; Rücker F.G.; Döhner K.; McGeehan G.M.; Levine R.L.; Bullinger L.; Vassiliou G.S.; Armstrong S.A.
发表日期	2020
ISSN	0036-8075
起始页码	586
结束页码	590
卷号	367 期号:6477
英文摘要	The initiating mutations that contribute to cancer development are sometimes present in premalignant cells. Whether therapies targeting these mutations can eradicate premalignant cells is unclear. Acute myeloid leukemia (AML) is an attractive system for investigating the effect of preventative treatment because this disease is often preceded by a premalignant state (clonal hematopoiesis or myelodysplastic syndrome). In Npm1c/Dnmt3a mutant knock-in mice, a model of AML development, leukemia is preceded by a period of extended myeloid progenitor cell proliferation and self-renewal. We found that this self-renewal can be reversed by oral administration of a small molecule (VTP-50469) that targets the MLL1-Menin chromatin complex. These preclinical results support the hypothesis that individuals at high risk of developing AML might benefit from targeted epigenetic therapy in a preventative setting. © 2020 American Association for the Advancement of Science. All rights reserved.
关键词	antileukemic agent methionine unclassified drug vtp 50469 biological development cancer cell disease treatment mutation numerical model oral health acute myeloid leukemia animal cell animal experiment animal model antineoplastic activity Article cell proliferation cell self-renewal chromatin controlled study drug targeting gene gene mutation leukemia cell molecularly targeted therapy mouse mouse model nonhuman NPM1 gene preleukemia priority journal Mus
语种	英语
来源机构	Science
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/133753
推荐引用方式 GB/T 7714	Uckelmann H.J.,Kim S.M.,Wong E.M.,et al. Therapeutic targeting of preleukemia cells in a mouse model of NPM1 mutant acute myeloid leukemia[J]. Science,2020,367(6477).
APA	Uckelmann H.J..,Kim S.M..,Wong E.M..,Hatton C..,Giovinazzo H..,...&Armstrong S.A..(2020).Therapeutic targeting of preleukemia cells in a mouse model of NPM1 mutant acute myeloid leukemia.,367(6477).
MLA	Uckelmann H.J.,et al."Therapeutic targeting of preleukemia cells in a mouse model of NPM1 mutant acute myeloid leukemia".367.6477(2020).