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OGP46 Induces Differentiation of Acute Myeloid Leukemia Cells via Different Optimal Signaling Pathways

Acute myelogenous leukemia (AML) is characterized by blockage of cell differentiation leading to the accumulation of immature cells, which is the most prevalent form of acute leukemia in adults. It is well known that all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) are the preferred drugs f...

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Autores principales: Zhao, Min, Wang, Jiangyun, Qu, Mei, Zhao, Yao, Wang, Haihua, Ke, Yu, Liu, Ying, Lei, Zi-Ning, Liu, Hong-Min, Hu, Zhenbo, Wei, Liuya, Chen, Zhe-Sheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969801/
https://www.ncbi.nlm.nih.gov/pubmed/33748146
http://dx.doi.org/10.3389/fcell.2021.652972
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author Zhao, Min
Wang, Jiangyun
Qu, Mei
Zhao, Yao
Wang, Haihua
Ke, Yu
Liu, Ying
Lei, Zi-Ning
Liu, Hong-Min
Hu, Zhenbo
Wei, Liuya
Chen, Zhe-Sheng
author_facet Zhao, Min
Wang, Jiangyun
Qu, Mei
Zhao, Yao
Wang, Haihua
Ke, Yu
Liu, Ying
Lei, Zi-Ning
Liu, Hong-Min
Hu, Zhenbo
Wei, Liuya
Chen, Zhe-Sheng
author_sort Zhao, Min
collection PubMed
description Acute myelogenous leukemia (AML) is characterized by blockage of cell differentiation leading to the accumulation of immature cells, which is the most prevalent form of acute leukemia in adults. It is well known that all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) are the preferred drugs for acute promyelocytic leukemia (APL). However, they can lead to irreversible resistance which may be responsible for clinical failure after complete remission (CR). Moreover, the differentiation therapy of ATRA-based treatment has not been effective against AML with t(8;21) translocation. Here we aimed to identify the differentiation effect of OGP46 on AML cell lines (HL-60, NB4, and Kasumi-1) and explore its possible mechanisms. We found that OGP46 has significant inhibitory activity against these cells by triggering cell differentiation with cell-cycle exit at G1/G0 and inhibited the colony-formation capacity of the AML cells. It was shown that OGP46 induced the differentiation of NB4 cells via the transcriptional misregulation in cancer signaling pathway by PML-RARα depletion, while it was attributed to the hematopoietic cell lineage and phagosome pathway in Kasumi-1 cells, which are all critical pathways in cell differentiation. These results highlight that OGP46 is an active agent not only in the APL cell line NB4 but also in AML-M2 cell lines, especially Kasumi-1 with t(8;21) translocation. Therefore, OGP46 may be a potential compound for surmounting the differentiation blockage in AML.
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spelling pubmed-79698012021-03-19 OGP46 Induces Differentiation of Acute Myeloid Leukemia Cells via Different Optimal Signaling Pathways Zhao, Min Wang, Jiangyun Qu, Mei Zhao, Yao Wang, Haihua Ke, Yu Liu, Ying Lei, Zi-Ning Liu, Hong-Min Hu, Zhenbo Wei, Liuya Chen, Zhe-Sheng Front Cell Dev Biol Cell and Developmental Biology Acute myelogenous leukemia (AML) is characterized by blockage of cell differentiation leading to the accumulation of immature cells, which is the most prevalent form of acute leukemia in adults. It is well known that all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) are the preferred drugs for acute promyelocytic leukemia (APL). However, they can lead to irreversible resistance which may be responsible for clinical failure after complete remission (CR). Moreover, the differentiation therapy of ATRA-based treatment has not been effective against AML with t(8;21) translocation. Here we aimed to identify the differentiation effect of OGP46 on AML cell lines (HL-60, NB4, and Kasumi-1) and explore its possible mechanisms. We found that OGP46 has significant inhibitory activity against these cells by triggering cell differentiation with cell-cycle exit at G1/G0 and inhibited the colony-formation capacity of the AML cells. It was shown that OGP46 induced the differentiation of NB4 cells via the transcriptional misregulation in cancer signaling pathway by PML-RARα depletion, while it was attributed to the hematopoietic cell lineage and phagosome pathway in Kasumi-1 cells, which are all critical pathways in cell differentiation. These results highlight that OGP46 is an active agent not only in the APL cell line NB4 but also in AML-M2 cell lines, especially Kasumi-1 with t(8;21) translocation. Therefore, OGP46 may be a potential compound for surmounting the differentiation blockage in AML. Frontiers Media S.A. 2021-03-04 /pmc/articles/PMC7969801/ /pubmed/33748146 http://dx.doi.org/10.3389/fcell.2021.652972 Text en Copyright © 2021 Zhao, Wang, Qu, Zhao, Wang, Ke, Liu, Lei, Liu, Hu, Wei and Chen. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Zhao, Min
Wang, Jiangyun
Qu, Mei
Zhao, Yao
Wang, Haihua
Ke, Yu
Liu, Ying
Lei, Zi-Ning
Liu, Hong-Min
Hu, Zhenbo
Wei, Liuya
Chen, Zhe-Sheng
OGP46 Induces Differentiation of Acute Myeloid Leukemia Cells via Different Optimal Signaling Pathways
title OGP46 Induces Differentiation of Acute Myeloid Leukemia Cells via Different Optimal Signaling Pathways
title_full OGP46 Induces Differentiation of Acute Myeloid Leukemia Cells via Different Optimal Signaling Pathways
title_fullStr OGP46 Induces Differentiation of Acute Myeloid Leukemia Cells via Different Optimal Signaling Pathways
title_full_unstemmed OGP46 Induces Differentiation of Acute Myeloid Leukemia Cells via Different Optimal Signaling Pathways
title_short OGP46 Induces Differentiation of Acute Myeloid Leukemia Cells via Different Optimal Signaling Pathways
title_sort ogp46 induces differentiation of acute myeloid leukemia cells via different optimal signaling pathways
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969801/
https://www.ncbi.nlm.nih.gov/pubmed/33748146
http://dx.doi.org/10.3389/fcell.2021.652972
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