All-trans retinoic acid (ATRA)-induced TFEB expression is required for myeloid differentiation in acute promyelocytic leukemia (APL)

Simple item page
dc.contributor.authorOrfali, Nina
dc.contributor.authorO'Donovan, Tracey R.
dc.contributor.authorCahill, Mary R.
dc.contributor.authorBenjamin, Dalyia
dc.contributor.authorNanus, David M.
dc.contributor.authorMcKenna, Sharon L.
dc.contributor.authorGudas, Lorraine J.
dc.contributor.authorMongan, Nigel P.
dc.contributor.funderBreakthrough Cancer Researchen
dc.contributor.funderHaematology Education and Research Trust, Irelanden
dc.contributor.funderNational Cancer Instituteen
dc.date.accessioned2023-03-16T12:32:15Z
dc.date.available2023-03-16T12:32:15Z
dc.date.issued2019-12-06
dc.date.updated2023-03-16T12:06:59Z
dc.description.abstractObjective: In acute promyelocytic leukemia (APL), normal retinoid signaling is disrupted by an abnormal PML-RAR alpha fusion oncoprotein, leading to a block in cell differentiation. Therapeutic concentrations of all-trans-retinoic acid (ATRA) can restore retinoid-induced transcription and promote degradation of the PML-RAR alpha protein. Autophagy is a catabolic pathway that utilizes lysosomal machinery to degrade intracellular material and facilitate cellular re-modeling. Recent studies have identified autophagy as an integral component of ATRA-induced myeloid differentiation.Methods: As the molecular communication between retinoid signaling and the autophagy pathway is not defined, we performed RNA sequencing of NB4 APL cells treated with ATRA and examined autophagy-related transcripts.Results: ATRA altered the expression of >80 known autophagy-related transcripts, including the key transcriptional regulator of autophagy and lysosomal biogenesis, TFEB (11.5-fold increase). Induction of TFEB and its transcriptional target, sequestosome 1 (SQSTM1, p62), is reduced in ATRA-resistant NB4R cells compared to NB4 cells. TFEB knockdown in NB4 cells alters the expression of transcriptional targets of TFEB and reduces CD11b transcript levels in response to ATRA.Conclusions: We show for the first time that TFEB plays an important role in ATRA-induced autophagy during myeloid differentiation and that autophagy induction potentiates leukemic cell differentiation (Note: this study includes data obtained from NCT00195156).en
dc.description.sponsorshipNational Cancer Institute (Grant/Award Number: R01CA043796)en
dc.description.statusPeer revieweden
dc.description.versionAccepted Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationOrfali, N., O'Donovan, T. R., Cahill, M. R., Benjamin, D., Nanus, D. M., McKenna, S. L., Gudas, L. J. and Mongan, N. P. (2019) 'All-trans retinoic acid (ATRA)-induced TFEB expression is required for myeloid differentiation in acute promyelocytic leukemia (APL)', European Journal of Haematology, 104(3), pp. 151-278. doi: 10.1111/ejh.13367en
dc.identifier.doi10.1111/ejh.13367en
dc.identifier.eissn1600-0609
dc.identifier.endpage278en
dc.identifier.issn0902-4441
dc.identifier.issued3en
dc.identifier.journaltitleEuropean Journal of Haematologyen
dc.identifier.startpage151en
dc.identifier.urihttps://hdl.handle.net/10468/14318
dc.identifier.volume104en
dc.language.isoenen
dc.publisherJohn Wiley & Sons, Inc.en
dc.rights© 2019, John Wiley & Sons Ltd. This is the accepted version of the following item: Orfali, N., O'Donovan, T. R., Cahill, M. R., Benjamin, D., Nanus, D. M., McKenna, S. L., Gudas, L. J. and Mongan, N. P. (2019) 'All-trans retinoic acid (ATRA)-induced TFEB expression is required for myeloid differentiation in acute promyelocytic leukemia (APL)', European Journal of Haematology, 104(3), pp. 151-278, doi: 10.1111/ejh.13367, which has been published in final form at: https://doi.org/10.1111/ejh.13367. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.en
dc.subjectAcute myeloid leukemiaen
dc.subjectAutophagyen
dc.subjectHematopoiesisen
dc.subjectDifferentiationen
dc.subjectRetinoiden
dc.subjectTranscription factor EBen
dc.titleAll-trans retinoic acid (ATRA)-induced TFEB expression is required for myeloid differentiation in acute promyelocytic leukemia (APL)en
dc.typeArticle (peer-reviewed)en
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
TFEB-EurJHaem-Feb2019.pdf
Size:
13.86 MB
Format:
Adobe Portable Document Format
Description:
Accepted Version
Download
License bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
license.txt
Size:
2.71 KB
Format:
Item-specific license agreed upon to submission
Description:
Download
Collections
Cancer Research @ UCC - Journal Articles