白血病干细胞与疾病的发生发展及其耐靶向药物紧密相连。申请者长期从事血液肿瘤干细胞调控、耐药和药物新靶点的研究，利用不同研究方法和平台，发现新的血液肿瘤细胞和干细胞的耐药机制。申请人主要成绩为：1.揭示TIGAR 揭示Alox5或15基因调控慢性髓细胞白血病（CML）干细胞耐药机制及作为药物新靶点；2. 发现SR-A基因调节CML干细胞活性；3. 揭示新药Omacetaxine对CML干细胞的作用及机制。相关成果发表在Nat Genet、JCI、Blood 、Leukemia等权威SCI杂志上，第一或通讯作者累计影响因子200+， 单篇他引最高110+次。入选江苏特聘教授和江苏特聘医学专家， 任中国生理学血液学专业委员会青年委员。申请人的前期工作发现TIGAR基因表达与 CML对激酶抑制剂耐药显著相关。本项目旨在阐明TIGAR在CML及CML干细胞中的功能和调控, 揭示其在CML发生中的作

Targeting of leukemia stem cells (LSCs) is believed to be essential for curative therapy of disease. The candidate has been studied the regulation of leukemia stem cells, target therapy resistance and identification of novel drug targets. By using the novel research platforms and methods, the candidate identified the novel mechanism and biomarkers of LSCs upon drug treatment. The candidate’s work showed: 1. Alox5 or Alox15 gene is required for chronic myeloid leukemia stem cell survival and Alox5 or Alox15 might be the novel drug targets for CML stem cells; 2. Msr-1 gene regulates the self-renew and differentiation of LSCs; 3. New CML drug Omacetaxine inhibits the survival of CML stem cells and its potential mechanism. The candidate’s work has been published on several high impact journals including Nature Genetics, JCI, Blood, Leukemia et. al. The total impact factors of candidate’s publications (first author corresponding author) are more than 200+ and the highest one is 110+. The candidate is funded by Jiangsu TePin Professor Program, Department of Education of Jiangsu Province and Jiangsu TePin Medical Expert Program, Health and Family Planning Commission of Jiangsu Province. The candidate also works as a Young Member of the Professional Committee of China physiology hematology. In preliminary study, we found that the expression of TIGAR gene is associated with CML resistant to TKIs treatment. This study will understand the role of TIGAR gene in regulating CML stem cell and CML development.