Downloads: 137

Files in This Item:
File Description SizeFormat 
s41598-017-16799-z.pdf2.29 MBAdobe PDFView/Open
Title: Autonomous feedback loop of RUNX1-p53-CBFB in acute myeloid leukemia cells
Authors: Morita, Ken
Noura, Mina
Tokushige, Chieko
Maeda, Shintaro
Kiyose, Hiroki
Kashiwazaki, Gengo
Taniguchi, Junichi
Bando, Toshikazu
Yoshida, Kenichi
Ozaki, Toshifumi
Matsuo, Hidemasa  kyouindb  KAKEN_id  orcid (unconfirmed)
Ogawa, Seishi  kyouindb  KAKEN_id
Liu, Pu Paul
Nakahata, Tatsutoshi
Sugiyama, Hiroshi  kyouindb  KAKEN_id
Adachi, Souichi
Kamikubo, Yasuhiko
Author's alias: 森田, 剣
能浦, 三奈
徳重, 智恵子
前田, 信太郎
清瀬, 大樹
柏﨑, 玄伍
谷口, 淳一
板東, 俊和
吉田, 健一
松尾, 英将
小川, 誠司
中畑, 龍俊
杉山, 弘
足立, 壯一
上久保, 靖彦
Keywords: Acute myeloid leukaemia
Issue Date: 30-Nov-2017
Publisher: Springer Nature
Journal title: Scientific Reports
Volume: 7
Thesis number: 16604
Abstract: Although runt-related transcription factor 1 (RUNX1) and its associating core binding factor-β (CBFB) play pivotal roles in leukemogenesis, and inhibition of RUNX1 has now been widely recognized as a novel strategy for anti-leukemic therapies, it has been elusive how leukemic cells could acquire the serious resistance against RUNX1-inhibition therapies and also whether CBFB could participate in this process. Here, we show evidence that p53 (TP53) and CBFB are sequentially up-regulated in response to RUNX1 depletion, and their mutual interaction causes the physiological resistance against chemotherapy for acute myeloid leukemia (AML) cells. Mechanistically, p53 induced by RUNX1 gene silencing directly binds to CBFB promoter and stimulates its transcription as well as its translation, which in turn acts as a platform for the stabilization of RUNX1, thereby creating a compensative RUNX1-p53-CBFB feedback loop. Indeed, AML cells derived from relapsed cases exhibited higher CBFB expression levels compared to those from primary AML cells at diagnosis, and these CBFB expressions were positively correlated to those of p53. Our present results underscore the importance of RUNX1-p53-CBFB regulatory loop in the development and/or maintenance of AML cells, which could be targeted at any sides of this triangle in strategizing anti-leukemia therapies.
Description: 急性骨髄性白血病の抗がん剤耐性メカニズム、一部解明. 京都大学プレスリリース. 2017-12-04.
Rights: © The Author(s) 2017
This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit
DOI(Published Version): 10.1038/s41598-017-16799-z
PubMed ID: 29192243
Related Link:
Appears in Collections:Journal Articles

Show full item record

Export to RefWorks

Export Format: 

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.