Ph+急性淋巴细胞白血病（Ph+ALL）治疗效果差，造血微环境的"庇护"作用是难以治愈的重要因素。申请者在前期基金课题中发现：连接蛋白43（CX43）介导的白血病骨髓基质间隙连接细胞间通讯（GJIC）功能缺失有助于白血病细胞残留并对化疗药物不敏感，但具体机制不明。CX43发挥作用与钙粘素（E-cadherin）关系密切，本研究拟在体外构建Ph+ALL骨髓基质细胞/SUP-B15细胞共培养残留耐药模型；研究骨髓基质细胞CX43与E-cadherin的相互作用及其对GJIC功能的影响；检测其对连接蛋白磷酸化和Ca+离子交换的作用效应；研究其通过BCR/ABL、β-catenin途径对Ph+ALL细胞增殖、凋亡的特殊影响；阐明由CX43/E-cadherin主导的骨髓基质GJIC功能与Ph+ALL残留耐药间的关系，从一新的角度探索Ph+ALL难治的原因和机制，为清除残留病降低复发奠定实验基础。

The effects of treatment on Ph + acute lymphoblastic leukemia(Ph + ALL) is poor.The "asylum"of Hematopoietic microenvironment on leukemia cells is a very important factor in refractory leukemia. Applicants in the preliminary research discovered that the dysfunction of gap junction intercellular communication（GJIC）in leukemia bone marrow stromal cells mediated by Connexin43（CX43）contributes to residual leukemia cells and the decreasing to chemotherapy sensitivity ,but the mechanism is not very clear by now. Since CX43 is closely related to cadherin, this study plans to build a residual disease model in vitro in which the bone marrow stromal cells from Ph + ALL patients are co-cultured with SUP-B15 cells , Using methods of co-immunoprecipitation,siRNA and laser confocal microscopy ect.to detect the Interactions of the complex of CX43/Cadher and the affect to GJIC's function ,to observe the effects to phosphorylation of connexin and Ca2+ flow, to probe into the influence to proliferation and apoptosis of Ph + ALL cells through the BCR / ABL, β-catenin Pathway, and to clarify the dynamic relationship between GJIC function and the residual leukemia mediated by CX43/cadherin. We investigate the study to research the causes and mechanisms of Ph + ALL refractory from a new angle, which may provide some experimental basis for the removal of minimal residual disease and reducing the relapse.