NFAT transcription factors are essential and redundant actors for leukemia initiating potential in T-cell acute lymphoblastic leukemia.

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy with few available targeted therapies. We previously reported that the phosphatase calcineurin (Cn) is required for LIC (leukemia Initiating Capacity) potential of T-ALL pointing to Cn as an interesting therapeutic target. Calci...

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Autores principales:	Claire Catherinet, Diana Passaro, Stéphanie Gachet, Hind Medyouf, Anne Reynaud, Charlène Lasgi, Jacques Ghysdael, Christine Tran Quang
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2035fe1092774cfca12dbb1b405d0995
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spelling	oai:doaj.org-article:2035fe1092774cfca12dbb1b405d09952021-12-02T20:15:35ZNFAT transcription factors are essential and redundant actors for leukemia initiating potential in T-cell acute lymphoblastic leukemia.1932-620310.1371/journal.pone.0254184https://doaj.org/article/2035fe1092774cfca12dbb1b405d09952021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0254184https://doaj.org/toc/1932-6203T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy with few available targeted therapies. We previously reported that the phosphatase calcineurin (Cn) is required for LIC (leukemia Initiating Capacity) potential of T-ALL pointing to Cn as an interesting therapeutic target. Calcineurin inhibitors have however unwanted side effect. NFAT transcription factors play crucial roles downstream of calcineurin during thymocyte development, T cell differentiation, activation and anergy. Here we elucidate NFAT functional relevance in T-ALL. Using murine T-ALL models in which Nfat genes can be inactivated either singly or in combination, we show that NFATs are required for T-ALL LIC potential and essential to survival, proliferation and migration of T-ALL cells. We also demonstrate that Nfat genes are functionally redundant in T-ALL and identified a node of genes commonly deregulated upon Cn or NFAT inactivation, which may serve as future candidate targets for T-ALL.Claire CatherinetDiana PassaroStéphanie GachetHind MedyoufAnne ReynaudCharlène LasgiJacques GhysdaelChristine Tran QuangPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 7, p e0254184 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Claire Catherinet Diana Passaro Stéphanie Gachet Hind Medyouf Anne Reynaud Charlène Lasgi Jacques Ghysdael Christine Tran Quang NFAT transcription factors are essential and redundant actors for leukemia initiating potential in T-cell acute lymphoblastic leukemia.
description	T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy with few available targeted therapies. We previously reported that the phosphatase calcineurin (Cn) is required for LIC (leukemia Initiating Capacity) potential of T-ALL pointing to Cn as an interesting therapeutic target. Calcineurin inhibitors have however unwanted side effect. NFAT transcription factors play crucial roles downstream of calcineurin during thymocyte development, T cell differentiation, activation and anergy. Here we elucidate NFAT functional relevance in T-ALL. Using murine T-ALL models in which Nfat genes can be inactivated either singly or in combination, we show that NFATs are required for T-ALL LIC potential and essential to survival, proliferation and migration of T-ALL cells. We also demonstrate that Nfat genes are functionally redundant in T-ALL and identified a node of genes commonly deregulated upon Cn or NFAT inactivation, which may serve as future candidate targets for T-ALL.
format	article
author	Claire Catherinet Diana Passaro Stéphanie Gachet Hind Medyouf Anne Reynaud Charlène Lasgi Jacques Ghysdael Christine Tran Quang
author_facet	Claire Catherinet Diana Passaro Stéphanie Gachet Hind Medyouf Anne Reynaud Charlène Lasgi Jacques Ghysdael Christine Tran Quang
author_sort	Claire Catherinet
title	NFAT transcription factors are essential and redundant actors for leukemia initiating potential in T-cell acute lymphoblastic leukemia.
title_short	NFAT transcription factors are essential and redundant actors for leukemia initiating potential in T-cell acute lymphoblastic leukemia.
title_full	NFAT transcription factors are essential and redundant actors for leukemia initiating potential in T-cell acute lymphoblastic leukemia.
title_fullStr	NFAT transcription factors are essential and redundant actors for leukemia initiating potential in T-cell acute lymphoblastic leukemia.
title_full_unstemmed	NFAT transcription factors are essential and redundant actors for leukemia initiating potential in T-cell acute lymphoblastic leukemia.
title_sort	nfat transcription factors are essential and redundant actors for leukemia initiating potential in t-cell acute lymphoblastic leukemia.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/2035fe1092774cfca12dbb1b405d0995
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NFAT transcription factors are essential and redundant actors for leukemia initiating potential in T-cell acute lymphoblastic leukemia.

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