多齿梳蛋白(Polycomb group complex, PcG)作为发挥转录抑制作用的重要表观遗传调控复合物，参与发育、衰老以及肿瘤发生等重要病生理过程，其成员众多，分为PRC1与PRC2复合物，各组分间既功能协同，又不失特性。PRC1中的CBX4以其独特的结构域而功能尤为特殊。前期工作发现在CML患者外周血中CBX4表达明显下调，而PcG经典靶基因HOX家族中的HOXA5则表现为上调，且给予伊马替尼治疗后，二者均向相反方向恢复，相似的变化趋势在AML患者骨髓以及MDS斑马鱼模型中也有发现。本研究拟以CML为切入点，深入研究CBX4和HOXA5与发病、进展与预后的关系；明确CBX4与HOXA5两者之间的作用机理；探索其与BCR-ABL1融合基因的关系; 进一步挖掘其下游的靶基因；为寻找可用于CML诊断以及预后评价的有效标志物提供证据，并为日后扩展到其他造血系统发育异常疾病提供参考。

Polycomb group complex (PcG), as the key transcriptional repressor, plays the important role in epigenetic regulation for target genes expression and are involved in development, senescence and tumorgenesis, etc. PcG consists of PRC1 and PRC2 which coordinate as well as present the distinct function for each individual. CBX4 is a representative component within PRC1. Our previous work found CBX4 was downregulated in CML peripheral blood. Upon Imatinib treatment, CBX4 restored to the normal level. As the canonical target of PcG, HOXA5 was found the opposite pattern-upregulated in CML and restored upon Imatinib treatment. This project is aiming to explore the relationship between CBX4/HOXA5 and CML diagnosis, progress and prognostics, further investigates the potential target of HOXA5, and provides the evidence for evaluating both CBX4 and HOXA5 as the potential biomarkers of CML and other types of leukemia.