对家族性白血病深入研究有助于揭示散发白血病发病机制。我们利用AML高发家系基因资源，克隆出FAMLF新基因，制备FAMLF抗体，验证其为编码蛋白基因，发现FAMLF基因及其内含子miR181a/b高表达于AML细胞，可能与细胞分化有关，是AML预后判断指标。但FAMLF基因及其miR181a/b在白血病发病机制中的作用未明。本项目将明确FAMLF基因在AML亚型表达谱及临床意义；明确FAMLF基因与miR181a/b分子水平上的相互作用关系；分别构建FAMLF基因及miR181a/b过表达与敲除的细胞模型，观测其对细胞增殖、细胞周期、分化、凋亡等的影响。从分子、细胞水平研究FAMLF基因的功能，以揭示FAMLF及其miR181a/b在白血病发病机制中的作用，为开发靶向药物奠定基础。

In-depth study of familial leukemia will help to clarify the mechanism underlying leukemogenesis in sporadic cases. A novel gene, FAMLF,was previously identified from patient in a unique AML-predisposed family.And the corresponding antibody was prepared to prove the existance of FAMLF as a protein-ecoding gene. We found that both FAMLF gene and it's intronic miR181a/b were overexpressed in some AML samples, related to cell differentiation, and can serve as a prognostic predictor. However, their roles in leukemogenesis remain obscure. Our study will aim at fully determining the expression signature of FAMLF in various subtypes of AML and further defining its clinical relevance; comfirming the molecular interaction between FAMLF gene and miR181a/b; constructing the cell models of FAMLF gene and miR181a/b up-regulated or down-regulated either independently or cooperatively to observe their influence on cell proliferation, differentiation and apoptosis; establishing the bone marrow transplantation mouse model of FAMLF gene overexpressed or knock-out to observe their influence on overal survival and bone marrow cell phenotypes of the mice as well as the tumorigenic effect on nude mice. The multi-level functional research of FAMLF gene and its intronic miRNA will reveal their roles in leukemogenesis ,and meanwhile provides the necessary theoretical basis for targed drugs development.