对肿瘤耐药机制和逆转策略的研究仍是目前热点。本课题旨在研究骨髓微环境中HO-1基因表达对血液肿瘤耐药的影响及机制。结果显示：① Real -time PCR和Western blot检测发现HO-1基因在血液肿瘤患者骨髓基质细胞（BMSCs）中高表达，可导致肿瘤耐药；② 慢病毒介导HO-1/siHO-1感染BMSCs，显示HO-1基因表达水平可影响共培养的肿瘤细胞耐药特性。③采用HO-1+/+，HO-1+/-基因敲除小鼠体内证实：肿瘤细胞在HO-1+/-组的耐药倍数低于HO-1+/+组。④ 通过激动剂及阻断剂方法研究，初步证实其耐药机制是通过JAK2/STAT5、CXCL12-CXCR4轴和HIF-1α等通路激活介导的。在下步研究中我们拟将采用二代测序、免疫共沉淀等在HO-1-/-敲除小鼠体内证实HO-1介导的肿瘤微环境耐药的机制和通路，为逆转肿瘤耐药提供新策略。

The mechanism and reversing strategy for tumor chemoresistance are still being spotlighted at present. This project aimed to explore the effects and mechanism of HO-1 expression in bone marrow microenvironment on hematological malignancies. The results showed us that: 1) Hematological tumor cells derived from clinical samples were insensitive to chemotherapeutic agents as HO-1 was overexpressed in bone marrow stromal cells (BMSCs) detected by real-time PCR and western blot. 2) Co-cultured hematological tumor cells and BMSCs were transfected by lenti-virus-HO-1/siHO-1, the tumor cells cocultured with HO-1 up-regulated the resistance of BMSCs to chemotherapeutic agents. 3) In vivo experiments showed that tumor cells in HO-1+/+ mice were more insensitive to chemothepeutic agents than those in HO-1+/- mice. 4) The drug-resistant mechanism mediated by HO-1 expressed in BMSCs involved in activation of JAK2/STAT5, CXCL12-CXCR4 axis and HIF-1α pathways. Nextly, we’ll verify the pathway induced by tumor microenvironment by second generation sequencing and co-immunoprecipitation, to supply a new strategy to reverse drug-resistance in hematological malignancy.