Dalyia N. Benjamin
All-Trans-Retinoic Acid Combined With Valproic Acid Can Promote Differentiation in Myeloid Leukemia Cells by an Autophagy Dependent Mechanism
Benjamin, Dalyia N.; O’Donovan, Tracey R.; Laursen, Kristian B.; Orfali, Nina; Cahill, Mary R.; Mongan, Nigel P.; Gudas, Lorraine J.; McKenna, Sharon L.
Authors
Tracey R. O’Donovan
Kristian B. Laursen
Nina Orfali
Mary R. Cahill
NIGEL MONGAN nigel.mongan@nottingham.ac.uk
Professor of Oncology
Lorraine J. Gudas
Sharon L. McKenna
Abstract
Acute myeloid leukemia (AML) is an aggressive blood cancer with an overall survival of 30%. One form of AML, acute promyelocytic leukemia (APL) has become more than 90% curable with differentiation therapy, consisting of all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO). Application of differentiation therapy to other AML subtypes would be a major treatment advance. Recent studies have indicated that autophagy plays a key role in the differentiation of ATRA-responsive APL cells. In this study, we have investigated whether differentiation could be enhanced in ATRA resistant cells by promoting autophagy induction with valproic acid (VPA). ATRA sensitive (NB4) and resistant leukemia cells (NB4R and THP-1) were co-treated with ATRA and valproic acid, followed by assessment of autophagy and differentiation. The combination of VPA and ATRA induced autophagic flux and promoted differentiation in ATRA-sensitive and -resistant cell lines. shRNA knockdown of ATG7 and TFEB autophagy regulators impaired both autophagy and differentiation, demonstrating the importance of autophagy in the combination treatment. These data suggest that ATRA combined with valproic acid can promote differentiation in myeloid leukemia cells by mechanism involving autophagy.
Citation
Benjamin, D. N., O’Donovan, T. R., Laursen, K. B., Orfali, N., Cahill, M. R., Mongan, N. P., …McKenna, S. L. (2022). All-Trans-Retinoic Acid Combined With Valproic Acid Can Promote Differentiation in Myeloid Leukemia Cells by an Autophagy Dependent Mechanism. Frontiers in Oncology, 12, Article 848517. https://doi.org/10.3389/fonc.2022.848517
Journal Article Type | Article |
---|---|
Acceptance Date | Jan 26, 2022 |
Online Publication Date | Feb 24, 2022 |
Publication Date | Feb 24, 2022 |
Deposit Date | Feb 26, 2022 |
Publicly Available Date | Feb 28, 2022 |
Journal | Frontiers in Oncology |
Electronic ISSN | 2234-943X |
Publisher | Frontiers Media |
Peer Reviewed | Peer Reviewed |
Volume | 12 |
Article Number | 848517 |
DOI | https://doi.org/10.3389/fonc.2022.848517 |
Keywords | Cancer Research; Oncology |
Public URL | https://nottingham-repository.worktribe.com/output/7509081 |
Publisher URL | https://www.frontiersin.org/articles/10.3389/fonc.2022.848517/full |
Files
2022 FrontierOnc
(10.4 Mb)
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Publisher Licence URL
https://creativecommons.org/licenses/by/4.0/
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