肿瘤相关巨噬细胞（TAM）介导微环境改变，调节肿瘤侵袭性是目前研究热点，我们前期研究发现酪氨酸激酶EphrinB2/EphB4信号启动TAM与急性髓系白血病（AML）细胞相互作用，是调节急性髓系白血病侵袭性的关键分子，从而推测出EphrinB2/EphB4诱导TAM调节AML侵袭机制的假说：TAM与AML细胞表面EphrinB2/EphB4信号的活化一方面能诱导TAM重塑骨髓造血微环境，为急性髓系白血病侵袭提供条件；另一方面能活化RhoA/Rac1/MMps，促进白血病细胞骨架改变、血管生成，从而直接促进急性髓系白血病细胞侵袭转移。我们利用急性髓系白血病原代细胞、细胞株和动物模型，通过细胞共培养、Ephrin-Eph配受体刺激实验、RNA干扰、Transwell侵袭实验等从体内外证实这一假说。这将为急性髓系白血病髓外浸润的治疗提供新的靶点，有利于解决急性髓系白血病难治、复发的难题。

Tumor associated macrophages (TAM) initiated regulation tumor invasion by mediation tumor microenvironment is the focus nowadays. Our previous study found that tyrosine kinase EphrinB2/EphB4 signal initiated interaction of TAM and acute myeloid leukemia (AML), which played an key role on acute myeloid leukemia invasiveness. Thus a hypothesis about how EphrinB2/EphB4 signal initiated TAM regulating invasion of AML was proposed: Activation of EphrinB2/EphB4 induced TAM remodeling hematopoietic stem cell (HSC) niches which would promote the invasion of acute myeloid leukemia, furthermore, the signaling pathway RhoA/Rac1/MMps were activated, causing leukemia cell cytoskeleton and angiogenesis , leading acute myeloid leukemia invasiveness and metastasis. Cell co-culture, Ephrin-Eph interaction tests , RNA interference and transwell invasion assay were used in primary leukemia cells，cell lines and animal models in vivo and in vitro respectively to validate the hypothesis. The results of this study will help to find new targets for the treatment of acute myeloid leukemia with extramedullary infiltration，but also conducive to further solve the problems at present of recurrent, refractory leukemia。