急性早幼粒细胞白血病中 PML/RARα 和 PU.1 对造血细胞激酶 (HCK) 的调控。

Regulation of the hematopoietic cell kinase (HCK) by PML/RARα and PU.1 in acute promyelocytic leukemia.

机构信息

State Key Laboratory of Medical Genomics, Rui-Jin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 197 Ruijin Rd II, Shanghai 200025, China.

出版信息

Leuk Res. 2012 Feb;36(2):219-23. doi: 10.1016/j.leukres.2011.09.012. Epub 2011 Oct 10.

DOI:10.1016/j.leukres.2011.09.012

PMID:21993313

Abstract

This study investigates the dynamic regulation of human hematopoietic cell kinase (HCK) in acute promyelocytic leukemia (APL) and the underlying molecular mechanisms. First, the level of HCK in APL blasts was found lower than that in normal granulocytes and monocytes. Second, the HCK promoter was repressed by PML/RARα and this repression required PU.1. PU.1 was capable of transactivating the HCK promoter through a region encompassing three PU.1 motifs. Chromatin immunoprecipitation assays provided evidence that PU.1 and PML/RARα bound to the HCK promoter in vivo. Finally, we found an unequivocal increase of HCK expression upon treatment with all-trans retinoic acid.

摘要

本研究探讨了人造血细胞激酶（HCK）在急性早幼粒细胞白血病（APL）中的动态调节及其潜在的分子机制。首先，发现 HCK 在 APL 原始细胞中的水平低于正常粒细胞和单核细胞。其次，PML/RARα 抑制 HCK 启动子，这种抑制需要 PU.1。PU.1 能够通过包含三个 PU.1 基序的区域反式激活 HCK 启动子。染色质免疫沉淀实验提供了证据表明 PU.1 和 PML/RARα 在体内结合到 HCK 启动子上。最后，我们发现全反式维甲酸治疗后 HCK 表达明显增加。