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

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.
AuthorsDandan Zou, Xianwen Yang, Yun Tan, Ping Wang, Xuehua Zhu, Wentao Yang, Xiaohong Jia, Ji Zhang, Kankan Wang
JournalLeukemia research (Leuk Res) Vol. 36 Issue 2 Pg. 219-23 (Feb 2012) ISSN: 1873-5835 [Electronic] England
PMID21993313 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2011 Elsevier Ltd. All rights reserved.
Chemical References
  • Antineoplastic Agents
  • Oncogene Proteins, Fusion
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • Trans-Activators
  • promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein
  • proto-oncogene protein Spi-1
  • Tretinoin
  • Luciferases
  • HCK protein, human
  • Proto-Oncogene Proteins c-hck
Topics
  • Antineoplastic Agents (pharmacology)
  • Blotting, Western
  • Cell Differentiation (drug effects)
  • Chromatin Immunoprecipitation
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Leukemia, Promyelocytic, Acute (drug therapy, genetics, metabolism)
  • Luciferases (metabolism)
  • Mutagenesis, Site-Directed
  • Mutation (genetics)
  • Oncogene Proteins, Fusion (genetics, metabolism)
  • Proto-Oncogene Proteins (genetics, metabolism)
  • Proto-Oncogene Proteins c-hck (genetics, metabolism)
  • RNA, Messenger (genetics)
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Trans-Activators (genetics, metabolism)
  • Tretinoin (pharmacology)
  • Tumor Cells, Cultured

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