RRC ID 50624
Author Morita K, Tokushige C, Maeda S, Kiyose H, Noura M, Iwai A, Yamada M, Kashiwazaki G, Taniguchi J, Bando T, Hirata M, Kataoka TR, Nakahata T, Adachi S, Sugiyama H, Kamikubo Y.
Title RUNX transcription factors potentially control E-selectin expression in the bone marrow vascular niche in mice.
Journal Blood Adv
Abstract Although the function of Runt-related (RUNX) transcription factors has been well characterized in leukemogenesis and regarded as an ideal target in antileukemia strategies, the effect of RUNX-inhibition therapy on bone marrow niche cells andr its impact on the engraftment of acute myeloid leukemia (AML) cells have largely been unknown. Here, we provide evidence suggesting the possible involvement of RUNX transcription factors in the transactivation of E-selectin, a member of selectin family of cell adhesion molecules, on the vascular endothelial cells of the mice bone marrow niche. In our experiments, gene switch-mediated silencing of RUNX downregulated E-selectin expression in the vascular niche and negatively controlled the engraftment of AML cells in the bone marrow, extending the overall survival of leukemic mice. Our work identified the novel role of RUNX family genes in the vascular niche and showed that the vascular niche, a home for AML cells, could be strategically targeted with RUNX-silencing antileukemia therapies. Considering the excellent efficacy of RUNX-inhibition therapy on AML cells themselves as we have previously reported, this strategy potentially targets AML cells both directly and indirectly, thus providing a better chance of cure for poor-prognostic AML patients.
Volume 2(5)
Pages 509-515
Published 2018-3-13
DOI 10.1182/bloodadvances.2017009324
PII bloodadvances.2017009324
PMID 29500219
PMC PMC5851413
MeSH Animals Blood Vessels / metabolism* Bone Marrow / blood supply* Core Binding Factor alpha Subunits / genetics Core Binding Factor alpha Subunits / physiology* E-Selectin / genetics* Endothelial Cells / metabolism Gene Expression Regulation Gene Silencing HEK293 Cells Human Umbilical Vein Endothelial Cells Humans Leukemia, Myeloid, Acute / etiology Leukemia, Myeloid, Acute / genetics Leukemia, Myeloid, Acute / pathology Mice Transcription Factors / physiology
Times Cited 4
Resource
DNA material pENTR4-H1tetOx1 (RDB07916) CS-RfA-ETBsd (RDB07917) CS-RfA-ETV (RDB08020) CS-RfA-ETR (RDB08362).