新近前白血病干细胞（pre-LSC）的研究，可能为急性白血病早期发生和复发提供全新机制。但由于缺乏能观察其直接向白血病完全转化的理想模型，pre-LSC的实质性特征及如何实现完全白血病转化的相关机制目前均难以明确。我们前期首次报道白血病微泡体外诱导正常造血细胞恶性转化为白血病细胞并可在体内外传代，极可能是能够展现造血干/祖细胞经pre-LSC向LSC及白血病细胞动态演进的创新体系。本项目拟采用高通量测序与我们前期建立的先进生物信息学方法，结合实验与临床验证，运用该体系来明确pre-LSC生物学特征，遴选并锁定调控其实现完全白血病转化的网络机制中的核心基因突变和异常信号通路。本项目有望为获取和研究pre-LSC、探索白血病多步骤发病机制提供创新性实验体系，为白血病的早期发生和复发提供预警标志物和精确干预靶标。

Recent reports of pre-leukemia stem cells (pre-LSCs) can provide fresh insight into the onset and relapse of acute leukemia(AL).Indificiency of models to observe complete transformation into leukemia, the distinct nature of pre-LSCs and how they transform to leukemia cells are remained to determined. We have, for the first time, successfully established a system in which microvesicles (MVs) derived from leukemia cells induce normal bone marrow hematopoietic cells to malignant transformation，leading to a full outbreak of leukemia within 20 days. And the induced leukemia cells can be passaged in vivo and vitro. This novel and specific system probably provide opportunities to observe and understand how multi-steps of clonal evolution, from normal hematopoietic stem progenitor cells(HSPC), to pre-LSC, to LSC and eventually to leukemic cells. Using this system, we will firstly determine the characteristics of pre-LSC using high-throughput parallel sequencing and bioinformatics analysis, then the key factors and pathway involved in the transformation of pre-LSCs to leukemia cells will be sorted out from the complex system that control the transformation of pre-LSCs to leukemia cells, which is next to be evaluated by lab experiments and clinical investigations. These works will contribute to clearly characterize the distinct nature of pre-LSCs and provide a key system for pre-LSC-related works and exploration of the underlying mechanisms of multi-steps pathogenesis of AL. Finally, the characterstics of pre-LSCs and sorted key node of the system will serve as markers and targets for the occurrence and recurrence of leukemia.