Gadd45γ是生长阻滞和DNA损伤诱导蛋白，对细胞生长发挥负向调控作用。我们在进行上一个国家自然科学基金项目研究癌基因Twist-1与髓系白血病发生发展关系时发现，Twist-1过表达可引起白血病细胞Gadd45γ表达显著下调。我们通过预实验证实Gadd45γ 低表达于急性髓系白血病(AML)患者骨髓及细胞系，初步功能验证发现Gadd45γ可能是AML新的肿瘤抑制基因。本课题即在此全新发现的基础上，(1) 明确Gadd45γ在AML患者中表达水平与患者临床特征的关系及其诊断、预后意义；(2) 搞清Gadd45γ在白血病细胞中的诱导表达模式；(3) 通过体内、体外实验证实Gadd45γ的抗白血病作用和作用机制; (4)阐明Gadd45γ在AML中低表达的机制。对上述问题的研究将为鉴定全新的白血病抑癌基因奠定基础，为阐明AML的发生机制提供新线索，为白血病的诊断、治疗、预后评估提供新的靶标。

Gadd45γ, a growth arrest DNA damage-inducible protein, plays essential roles in negative regulation of cell proliferation. While exploring the role of oncogene Twist-1 in the development of myeloid leukemia, supported by the National Natural Science Foundation of China, we found that enforced expression of Twist-1 in leukemic cells led to significant inhibition of Gadd45γ. Further evidence indicates that Gadd45γ is downregulated in acute myeloid leukemia (AML) cells and may function as an anti-oncogene in AML. Based on these novel findings, we plan to conduct the following investigations to elucidate the role of Gadd45γ in AML and its mechanism. 1. Explore the association of the expression level of Gadd45γ with the AML patients’ clinical characteristics and the diagnostic and prognostic role of GADD45γ in AML. 2. Investigate the inducers of Gadd45γ in leukemic cells. 3. Evaluate the anti-cancer effect and its mechanism of Gadd45γ on AML through in vitro and in vivo studies. 4. Elucidate the mechanism of the dysregulation of Gadd45γ in AML. The accomplishment of this project may characterize novel anti-oncogene, provide new clues for elucidating the mechanism underlying the pathogenesis of AML, and discover new target for improving diagnosis and risk and treatment stratification in AML.