白血病状态下正常造血干/祖细胞的生物学行为及其调控机制:国家自然科学基金重大项目结题综述

Final report on the major program of NSFC—“Biological Behaviors and Regulatory Mechanisms of Normal Hematopoietic Stem/Progenitor Cells during the Development of Leukemia”

国家自然科学基金"十二五"重大项目"白血病状态下正常造血干/祖细胞的生物学行为及其调控机制"集中围绕正常造血干/祖细胞在白血病状态下的受抑规律及其内外调控机制这一热点科学问题进行了多团队联合攻关。经过2011—2014年的4年研究,从分子、细胞、整体和临床等多个层面系统阐释了白血病状态下白血病细胞和正常造血干/祖细胞竞争的规律,揭示了白血病恶性克隆生长和正常造血干/祖细胞受抑的分子机制,提出了抑制白血病细胞特别是白血病干细胞生长及促进正常造血干/祖细胞扩增的治疗新策略,取得了一系列突破性和原创性的研究成果,为进一步提高白血病临床治疗效果奠定了重要基础。

The major program of ＂Biological Behaviors and Regulatory Mechanisms of Normal Hematopoi- etic Stem/Progenitor Cells during the Development of Leukemia＂ mainly focuses on the mechanisms under- lying the competition between normal hematopoietic stem/progenitor cell （HSC/HPC） and leukemic cells. Upon a 4-year study by the four collaborative groups, significant progress has been made in the following areas： （1） optimized and established several unique leukemia models~ （2） systemically studied the kinetics of normal HSC/HPC and altered micro-environmental elements during leukemia development; （3） defined several novel genetic and epigenetic regulators that govern the competition between HSC/HPCs and LSCs during leukemia development; （4） discovered several novel small molecules that can promote normal HSC/ HPC expansion or inhibit leukemia cell proliferation. These results would help better understand the path- ogenesis or current therapies of leukemia and provide novel therapeutic strategies to combat the disease.