A genetic screen in Drosophila uncovers the multifaceted properties of the NUP98-HOXA9 oncogene.

Acute myeloid leukemia (AML) underlies the uncontrolled accumulation of immature myeloid blasts. Several cytogenetic abnormalities have been associated with AML. Among these is the NUP98-HOXA9 (NA9) translocation that fuses the Phe-Gly repeats of nucleoporin NUP98 to the homeodomain of the transcrip...

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Autores principales:	Gwenaëlle Gavory, Caroline Baril, Gino Laberge, Gawa Bidla, Surapong Koonpaew, Thomas Sonea, Guy Sauvageau, Marc Therrien
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Genetics QH426-470
Acceso en línea:	https://doaj.org/article/1022a849084a400b940c491612d3321d
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spelling	oai:doaj.org-article:1022a849084a400b940c491612d3321d2021-12-02T20:02:53ZA genetic screen in Drosophila uncovers the multifaceted properties of the NUP98-HOXA9 oncogene.1553-73901553-740410.1371/journal.pgen.1009730https://doaj.org/article/1022a849084a400b940c491612d3321d2021-08-01T00:00:00Zhttps://doi.org/10.1371/journal.pgen.1009730https://doaj.org/toc/1553-7390https://doaj.org/toc/1553-7404Acute myeloid leukemia (AML) underlies the uncontrolled accumulation of immature myeloid blasts. Several cytogenetic abnormalities have been associated with AML. Among these is the NUP98-HOXA9 (NA9) translocation that fuses the Phe-Gly repeats of nucleoporin NUP98 to the homeodomain of the transcription factor HOXA9. The mechanisms enabling NA9-induced leukemia are poorly understood. Here, we conducted a genetic screen in Drosophila for modifiers of NA9. The screen uncovered 29 complementation groups, including genes with mammalian homologs known to impinge on NA9 activity. Markedly, the modifiers encompassed a diversity of functional categories, suggesting that NA9 perturbs multiple intracellular events. Unexpectedly, we discovered that NA9 promotes cell fate transdetermination and that this phenomenon is greatly influenced by NA9 modifiers involved in epigenetic regulation. Together, our work reveals a network of genes functionally connected to NA9 that not only provides insights into its mechanism of action, but also represents potential therapeutic targets.Gwenaëlle GavoryCaroline BarilGino LabergeGawa BidlaSurapong KoonpaewThomas SoneaGuy SauvageauMarc TherrienPublic Library of Science (PLoS)articleGeneticsQH426-470ENPLoS Genetics, Vol 17, Iss 8, p e1009730 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Genetics QH426-470
spellingShingle	Genetics QH426-470 Gwenaëlle Gavory Caroline Baril Gino Laberge Gawa Bidla Surapong Koonpaew Thomas Sonea Guy Sauvageau Marc Therrien A genetic screen in Drosophila uncovers the multifaceted properties of the NUP98-HOXA9 oncogene.
description	Acute myeloid leukemia (AML) underlies the uncontrolled accumulation of immature myeloid blasts. Several cytogenetic abnormalities have been associated with AML. Among these is the NUP98-HOXA9 (NA9) translocation that fuses the Phe-Gly repeats of nucleoporin NUP98 to the homeodomain of the transcription factor HOXA9. The mechanisms enabling NA9-induced leukemia are poorly understood. Here, we conducted a genetic screen in Drosophila for modifiers of NA9. The screen uncovered 29 complementation groups, including genes with mammalian homologs known to impinge on NA9 activity. Markedly, the modifiers encompassed a diversity of functional categories, suggesting that NA9 perturbs multiple intracellular events. Unexpectedly, we discovered that NA9 promotes cell fate transdetermination and that this phenomenon is greatly influenced by NA9 modifiers involved in epigenetic regulation. Together, our work reveals a network of genes functionally connected to NA9 that not only provides insights into its mechanism of action, but also represents potential therapeutic targets.
format	article
author	Gwenaëlle Gavory Caroline Baril Gino Laberge Gawa Bidla Surapong Koonpaew Thomas Sonea Guy Sauvageau Marc Therrien
author_facet	Gwenaëlle Gavory Caroline Baril Gino Laberge Gawa Bidla Surapong Koonpaew Thomas Sonea Guy Sauvageau Marc Therrien
author_sort	Gwenaëlle Gavory
title	A genetic screen in Drosophila uncovers the multifaceted properties of the NUP98-HOXA9 oncogene.
title_short	A genetic screen in Drosophila uncovers the multifaceted properties of the NUP98-HOXA9 oncogene.
title_full	A genetic screen in Drosophila uncovers the multifaceted properties of the NUP98-HOXA9 oncogene.
title_fullStr	A genetic screen in Drosophila uncovers the multifaceted properties of the NUP98-HOXA9 oncogene.
title_full_unstemmed	A genetic screen in Drosophila uncovers the multifaceted properties of the NUP98-HOXA9 oncogene.
title_sort	genetic screen in drosophila uncovers the multifaceted properties of the nup98-hoxa9 oncogene.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/1022a849084a400b940c491612d3321d
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A genetic screen in Drosophila uncovers the multifaceted properties of the NUP98-HOXA9 oncogene.

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