The tyrosine kinase inhibitor dasatinib induces a marked adipogenic differentiation of human multipotent mesenchymal stromal cells.

<h4>Background</h4>The introduction of specific BCR-ABL inhibitors in chronic myelogenous leukemia therapy has entirely mutated the prognosis of this hematologic cancer from being a fatal disorder to becoming a chronic disease. Due to the probable long lasting treatment with tyrosine-kin...

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Autores principales:	Adriana Borriello, Ilaria Caldarelli, Maria Assunta Basile, Debora Bencivenga, Annunziata Tramontano, Silverio Perrotta, Fulvio Della Ragione, Adriana Oliva
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/16c48b6ed8714db89955d42804853f88
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spelling	oai:doaj.org-article:16c48b6ed8714db89955d42804853f882021-11-18T07:33:04ZThe tyrosine kinase inhibitor dasatinib induces a marked adipogenic differentiation of human multipotent mesenchymal stromal cells.1932-620310.1371/journal.pone.0028555https://doaj.org/article/16c48b6ed8714db89955d42804853f882011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22164306/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>The introduction of specific BCR-ABL inhibitors in chronic myelogenous leukemia therapy has entirely mutated the prognosis of this hematologic cancer from being a fatal disorder to becoming a chronic disease. Due to the probable long lasting treatment with tyrosine-kinase inhibitors (TKIs), the knowledge of their effects on normal cells is of pivotal importance.<h4>Design and methods</h4>We investigated the effects of dasatinib treatment on human bone marrow-derived mesenchymal stromal cells (MSCs).<h4>Results</h4>Our findings demonstrate, for the first time, that dasatinib induces MSCs adipocytic differentiation. Particularly, when the TKI is added to the medium inducing osteogenic differentiation, a high MSCs percentage acquires adipocytic morphology and overexpresses adipocytic specific genes, including PPARγ, CEBPα, LPL and SREBP1c. Dasatinib also inhibits the activity of alkaline phosphatase, an osteogenic marker, and remarkably reduces matrix mineralization. The increase of PPARγ is also confirmed at protein level. The component of osteogenic medium required for dasatinib-induced adipogenesis is dexamethasone. Intriguingly, the increase of adipocytic markers is also observed in MSCs treated with dasatinib alone. The TKI effect is phenotype-specific, since fibroblasts do not undergo adipocytic differentiation or PPARγ increase.<h4>Conclusions</h4>Our data demonstrate that dasatinib treatment affects bone marrow MSCs commitment and suggest that TKIs therapy might modify normal phenotypes with potential significant negative consequences.Adriana BorrielloIlaria CaldarelliMaria Assunta BasileDebora BencivengaAnnunziata TramontanoSilverio PerrottaFulvio Della RagioneAdriana OlivaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 12, p e28555 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Adriana Borriello Ilaria Caldarelli Maria Assunta Basile Debora Bencivenga Annunziata Tramontano Silverio Perrotta Fulvio Della Ragione Adriana Oliva The tyrosine kinase inhibitor dasatinib induces a marked adipogenic differentiation of human multipotent mesenchymal stromal cells.
description	<h4>Background</h4>The introduction of specific BCR-ABL inhibitors in chronic myelogenous leukemia therapy has entirely mutated the prognosis of this hematologic cancer from being a fatal disorder to becoming a chronic disease. Due to the probable long lasting treatment with tyrosine-kinase inhibitors (TKIs), the knowledge of their effects on normal cells is of pivotal importance.<h4>Design and methods</h4>We investigated the effects of dasatinib treatment on human bone marrow-derived mesenchymal stromal cells (MSCs).<h4>Results</h4>Our findings demonstrate, for the first time, that dasatinib induces MSCs adipocytic differentiation. Particularly, when the TKI is added to the medium inducing osteogenic differentiation, a high MSCs percentage acquires adipocytic morphology and overexpresses adipocytic specific genes, including PPARγ, CEBPα, LPL and SREBP1c. Dasatinib also inhibits the activity of alkaline phosphatase, an osteogenic marker, and remarkably reduces matrix mineralization. The increase of PPARγ is also confirmed at protein level. The component of osteogenic medium required for dasatinib-induced adipogenesis is dexamethasone. Intriguingly, the increase of adipocytic markers is also observed in MSCs treated with dasatinib alone. The TKI effect is phenotype-specific, since fibroblasts do not undergo adipocytic differentiation or PPARγ increase.<h4>Conclusions</h4>Our data demonstrate that dasatinib treatment affects bone marrow MSCs commitment and suggest that TKIs therapy might modify normal phenotypes with potential significant negative consequences.
format	article
author	Adriana Borriello Ilaria Caldarelli Maria Assunta Basile Debora Bencivenga Annunziata Tramontano Silverio Perrotta Fulvio Della Ragione Adriana Oliva
author_facet	Adriana Borriello Ilaria Caldarelli Maria Assunta Basile Debora Bencivenga Annunziata Tramontano Silverio Perrotta Fulvio Della Ragione Adriana Oliva
author_sort	Adriana Borriello
title	The tyrosine kinase inhibitor dasatinib induces a marked adipogenic differentiation of human multipotent mesenchymal stromal cells.
title_short	The tyrosine kinase inhibitor dasatinib induces a marked adipogenic differentiation of human multipotent mesenchymal stromal cells.
title_full	The tyrosine kinase inhibitor dasatinib induces a marked adipogenic differentiation of human multipotent mesenchymal stromal cells.
title_fullStr	The tyrosine kinase inhibitor dasatinib induces a marked adipogenic differentiation of human multipotent mesenchymal stromal cells.
title_full_unstemmed	The tyrosine kinase inhibitor dasatinib induces a marked adipogenic differentiation of human multipotent mesenchymal stromal cells.
title_sort	tyrosine kinase inhibitor dasatinib induces a marked adipogenic differentiation of human multipotent mesenchymal stromal cells.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/16c48b6ed8714db89955d42804853f88
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The tyrosine kinase inhibitor dasatinib induces a marked adipogenic differentiation of human multipotent mesenchymal stromal cells.

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