美国丹娜-法伯癌症研究所Scott A. Armstrong研究小组的近期工作发现，NPM1突变型急性髓细胞白血病小鼠模型中的前白血病细胞可被治疗性靶向。2020年1月31日，这一研究成果发表在国际学术期刊《科学》上。

据研究人员介绍，促进癌症进展的起始突变有时存在于癌前细胞中。目前还不清楚靶向这些突变的疗法是否能够根除癌前细胞。急性髓细胞白血病（AML）是研究预防性治疗方法的有效系统，因为该疾病通常伴有恶变前状态（克隆性造血或骨髓增生异常综合征）。在Npm1c/Dnmt3a突变型敲入小鼠中（AML发生模型），在白血病发生之前，髓系祖细胞的增殖和自我更新会持续一段时间。

研究人员发现，这种自我更新可以通过口服靶向MLL1-Menin染色质复合物的小分子（VTP-50469）来逆转。这些临床前结果表明，在预防性背景下，罹患AML的高风险个体可能会从靶向表观遗传的治疗中受益。

附：英文原文

Title: Therapeutic targeting of preleukemia cells in a mouse model of NPM1 mutant acute myeloid leukemia

Author: Hannah J. Uckelmann, Stephanie M. Kim, Eric M. Wong, Charles Hatton, Hugh Giovinazzo, Jayant Y. Gadrey, Andrei V. Krivtsov, Frank G. Rücker, Konstanze Dhner, Gerard M. McGeehan, Ross L. Levine, Lars Bullinger, George S. Vassiliou, Scott A. Armstrong

Issue&Volume: 2020/01/31

Abstract: 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.

DOI: 10.1126/science.aax5863

Source: https://science.sciencemag.org/content/367/6477/586