cbx4在巨噬细胞发育及急性单核白血病中的机制研究

PRC1作为发挥转录抑制作用的重要表观遗传调控复合物，在胚胎发育和各个生命活动中具 有重要作用。已有研究报道某些白血病患者中常伴有PRC1某些成员的异常表达或突变，然而， 由于PCR1复合物组成复杂，家族成员众多，各成员之间功能协同而不失特性，CBX4作为PCR1成 员之一，目前在造血调控及白血病中的研究鲜有报道。我们已掌握的数据提示CBX4可能参与造血调控与白血病形成，因此本项目拟利用斑马鱼为模式动物，研究CBX4在造血及白血病发生发展中的作用。通过前期的研究，发现以下研究线索：1.NCBI数据库显示CBX4 主要高表达在人类造血相关组织。2.部分AML临床样本中CBX4的显著升高。3.cbx4在斑马鱼巨噬细胞及淋巴细胞中高表达。4.cbx4突变体幼鱼中巨噬细胞减少，而在cbx4过表达斑马鱼中巨噬细胞增多， 成年cbx4过表达斑马鱼中巨噬细胞、前体细胞增多，出现类似AML-M5样表型。

PRC1 plays a pivotal role in embryonic development and various life activities as an important epigenetic regulatory complex with transcriptional inhibitory function. It has been reported that some leukemia patients are often accompanied by abnormal expression or mutation of members of PRC1. However, due to the complex composition and large number of PCR1 and their various functions, CBX4 had not been reported to involved in hematopoiesis and leukemia. Our previous data suggest that CBX4 may be involved in hematopoietic regulation and leukemia formation. Therefore, this project intends to use zebrafish as a animal model.to study the role of CBX4 in hematopoiesis and leukemia development. Through our previous studies, the following clues were found: 1. CBX4 is found to be highly expressed in human hematopoietic related tissues in NCBI database. 2. There was a significant increase of CBX4 in some clinical samples of leukemia. 3. Cbx4 is highly expressed in macrophages and lymphocytes in zebrafish. 4. Macrophages were decreased in juvenile cbx4 mutant zebrafish, while increased in cbx4 overexpression zebrafish..5. Macrophages and precursors were increased in adult cbx4 overexpression zebrafish and exhibit a AML-M5 like phenotype.