Combined staurosporine and retinoic acid induces differentiation in retinoic acid resistant acute promyelocytic leukemia cell lines

All-trans retinoic acid (ATRA) resistance has been a critical problem in acute promyelocytic leukemia (APL) relapsed patients. In ATRA resistant APL cell lines NB4-R1 and NB4-R2, the combination of staurosporine and ATRA synergized to trigger differentiation accompanied by significantly enhanced pro...

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Main Authors:	Ge, Dong-zheng, Sheng, Yan, Cai, Xun
Format:	Online
Language:	English
Published:	Nature Publishing Group 2014
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4001092/

id	pubmed-4001092
recordtype	oai_dc
spelling	pubmed-40010922014-04-28 Combined staurosporine and retinoic acid induces differentiation in retinoic acid resistant acute promyelocytic leukemia cell lines Ge, Dong-zheng Sheng, Yan Cai, Xun Article All-trans retinoic acid (ATRA) resistance has been a critical problem in acute promyelocytic leukemia (APL) relapsed patients. In ATRA resistant APL cell lines NB4-R1 and NB4-R2, the combination of staurosporine and ATRA synergized to trigger differentiation accompanied by significantly enhanced protein level of CCAAT/enhancer binding protein ε (C/EBPε) and C/EBPβ as well as the phosphorylation of mitogen-activated protein (MEK) and extracellular signal-regulated kinase (ERK). Furthermore, attenuation of the MEK activation blocked not only the differentiation but also the increased protein level of C/EBPε and C/EBPβ. Taken together, we concluded that the combination of ATRA and staurosporine could overcome differentiation block via MEK/ERK signaling pathway in ATRA-resistant APL cell lines. Nature Publishing Group 2014-04-28 /pmc/articles/PMC4001092/ /pubmed/24769642 http://dx.doi.org/10.1038/srep04821 Text en Copyright © 2014, Macmillan Publishers Limited. All rights reserved http://creativecommons.org/licenses/by-nc-nd/3.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. The images in this article are included in the article's Creative Commons license, unless indicated otherwise in the image credit; if the image is not included under the Creative Commons license, users will need to obtain permission from the license holder in order to reproduce the image. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Ge, Dong-zheng Sheng, Yan Cai, Xun
spellingShingle	Ge, Dong-zheng Sheng, Yan Cai, Xun Combined staurosporine and retinoic acid induces differentiation in retinoic acid resistant acute promyelocytic leukemia cell lines
author_facet	Ge, Dong-zheng Sheng, Yan Cai, Xun
author_sort	Ge, Dong-zheng
title	Combined staurosporine and retinoic acid induces differentiation in retinoic acid resistant acute promyelocytic leukemia cell lines
title_short	Combined staurosporine and retinoic acid induces differentiation in retinoic acid resistant acute promyelocytic leukemia cell lines
title_full	Combined staurosporine and retinoic acid induces differentiation in retinoic acid resistant acute promyelocytic leukemia cell lines
title_fullStr	Combined staurosporine and retinoic acid induces differentiation in retinoic acid resistant acute promyelocytic leukemia cell lines
title_full_unstemmed	Combined staurosporine and retinoic acid induces differentiation in retinoic acid resistant acute promyelocytic leukemia cell lines
title_sort	combined staurosporine and retinoic acid induces differentiation in retinoic acid resistant acute promyelocytic leukemia cell lines
description	All-trans retinoic acid (ATRA) resistance has been a critical problem in acute promyelocytic leukemia (APL) relapsed patients. In ATRA resistant APL cell lines NB4-R1 and NB4-R2, the combination of staurosporine and ATRA synergized to trigger differentiation accompanied by significantly enhanced protein level of CCAAT/enhancer binding protein ε (C/EBPε) and C/EBPβ as well as the phosphorylation of mitogen-activated protein (MEK) and extracellular signal-regulated kinase (ERK). Furthermore, attenuation of the MEK activation blocked not only the differentiation but also the increased protein level of C/EBPε and C/EBPβ. Taken together, we concluded that the combination of ATRA and staurosporine could overcome differentiation block via MEK/ERK signaling pathway in ATRA-resistant APL cell lines.
publisher	Nature Publishing Group
publishDate	2014
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4001092/
_version_	1612082895433760768

Combined staurosporine and retinoic acid induces differentiation in retinoic acid resistant acute promyelocytic leukemia cell lines

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