急性髓系白血病（AML）化疗已取得较大进展，但耐药仍严重影响患者治疗及生存。骨髓微环境中存在独特的氨基酸微环境，在造血干细胞的自我维持中发挥重要作用，且骨髓微环境半胱氨酸代谢异常在CLL耐药中发挥重要作用。我们前期研究结果显示半胱氨酸代谢产物硫化氢参与AML耐药，因此我们推测AML患者骨髓微环境半胱氨酸代谢异常可能在AML耐药中发挥重要作用。本课题拟检测初诊和复发难治AML患者化疗前后骨髓微环境中胱氨酸/半胱氨酸含量；观察半胱氨酸对AML细胞药物敏感性的影响；研究半胱氨酸产物硫化氢及其相关靶基因，阐明半胱氨酸/硫化氢参与AML耐药的具体作用机制；利用CSE基因敲除小鼠及C57BL/6小鼠构建AML小鼠模型，体内研究半胱氨酸/硫化氢介导AML耐药的作用及其具体机制。预期目标的实现将揭示骨髓氨基酸微环境介导AML耐药的新机制，对克服AML耐药、清除微小残留病变具有重要意义。

Great progress has been made in the chemotherapy of acute myeloid leukemia (AML). However, chemo-resistance severely impairs treatment efficiency and survival. A specialized amino acid microenvironment existed in bone marrow microenvironment， which is indispensable for the proliferation and maintenance of hematopoietic stem cell. Previously study verified that stromal control of cystine metabolism promoted cancer cell survival in chronic lymphocytic leukemia. Our previous study has shown that hydrogen sulfide, a metabolite of cystine, contributed to AML chemo-resistance. We speculated cysteine metabolic abnormality in bone marrow microenvironment mediated chemo-resistance in AML. In the following study, we intend to detect cystine/cysteine in the bone marrow microenvironment of newly diagnose and refractory AML patients. Then observe the effects of cysteine on drug sensitivity of AML cells and investigate the down-stream signaling pathways associated with cysteine/hydrogen sulfide. We will further determine the effects of cysteine/hydrogen sulfide on AML chemo-resistance in the CSE knockout and C57BL/6 mouse models engrafted with AML cells. Our study is of great importance in overcoming drug resistance and eliminating minimal residual disease in AML.