去甲基化药物地西他滨可用于慢性粒细胞白血病（CML）的治疗，但介导其抗CML作用的重要基因尚不清楚。地西他滨与伊马替尼具有协同抗CML作用，作用机制亦未阐明。我们在进行上一个国家自然基金课题时首次发现白血病患者中小分子热休克蛋白HSPB8启动子处于高度甲基化状态，HSPB8可被地西他滨诱导表达，过表达HSPB8具有抗CML作用，并可增强CML细胞对伊马替尼的敏感性，已发表SCI收录论文。本课题在前期发现的基础上拟：1. 探讨HSPB8是否在地西他滨抗CML中发挥重要作用；2. 搞清HSPB8在地西他滨与伊马替尼协同抗白血病效果中所起的作用和机制。对上述问题的探索，将可能为找到地西他滨去甲基化治疗CML的分子标志物奠定基础，为阐明地西他滨和伊马替尼协同抗白血病作用机制提供线索，为临床应用更有效针对CML的治疗方案提供理论依据。

Decitabine is a demethylating agent and has become a treatment for chronic myelogenous leukemia (CML). The critical gene through which decitabine exerts anti-leukemia effect is still unknown. Combinatorial delivery of decitabine and imatinib synergize to confer superior therapeutic effect, but the underlying mechanism remains elusive. While carrying out the last National Natural Science Foundation of China, we found that promoter DNA of HSPB8 was methylated in hematopoietic tumor cell lines, primary patients and normal volunteer samples. HSPB8 expression could be restored after demethylation treatment with decitabine. Overexpression of HSPB8 exerted anti-leukemia effect, and enhanced imatinib mesylate-induced apoptosis in CML cell line. These data has been published in SCI journal. Based on these findings, we intend to investigate whether HSPB8 plays an important role in the anti-CML effect mediated by decitabine; further verify the ability of HSPB8 in enhancing the sensitivity of CML cell line to imatinib; elucidate the function of HSPB8 in the synergistic effect of decitabine and imatinib in CML therapy. The accomplishment of this project may lay a foundation for finding the molecular marker for demethylation therapies, provide clues for elucidating the mechanism underlying the synergistic effect of decitabine and imatinib, and provide theoretical basis for choosing more efficacious therapy for CML.