De novo AML exhibits greater microenvironment dysregulation compared to AML with myelodysplasia-related changes
Autor(a) principal: | |
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Data de Publicação: | 2017 |
Outros Autores: | , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNIFESP |
Texto Completo: | https://repositorio.unifesp.br/handle/11600/55258 http://dx.doi.org/10.1038/srep40707 |
Resumo: | The interaction between the bone marrow microenvironment and malignant hematopoietic cells can result in the protection of leukemia cells from chemotherapy in both myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). We, herein, characterized the changes in cytokine expression and the function of mesenchymal stromal cells (MSC) in patients with MDS, AML with myelodysplasia-related changes (MRC), a well-recognized clinical subtype of secondary AML, and de novo AML. We observed a significant inhibitory effect of MDS-MSC on T-lymphocyte proliferation and no significant differences in any of the cytokines tested. AML-MSC inhibited T-cell proliferation only at a very low MSC/T cell ratio. When compared to the control, AML-MRC-derived MSC presented a significant increase in IL6 expression, whereas de novo AML MSC presented a significant increase in the expression levels of VEGFA, CXCL12, RPGE2, IDO, IL1 beta, IL6 and IL32, followed by a decrease in IL10 expression. Furthermore, data indicate that IL-32 regulates stromal cell proliferation, has a chemotactic potential and participates in stromal cell crosstalk with leukemia cells, which could result in chemoresistance. Our results suggest that the differences between AML-MRC and de novo AML also extend into the leukemic stem cell niche and that IL-32 can participate in the regulation of the bone marrow cytokine milieu. |
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Lopes, Matheus RodriguesNovais Pereira, Joao KleberCampos, Paula de MeloMachado-Neto, Joao AgostinhoTraina, FabiolaOlalla Saad, Sara T.Favaro, Patricia [UNIFESP]2020-07-17T14:03:15Z2020-07-17T14:03:15Z2017Scientific Reports. London, v. 7, p. -, 2017.2045-2322https://repositorio.unifesp.br/handle/11600/55258http://dx.doi.org/10.1038/srep40707WOS000391927200001.pdf10.1038/srep40707WOS:000391927200001The interaction between the bone marrow microenvironment and malignant hematopoietic cells can result in the protection of leukemia cells from chemotherapy in both myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). We, herein, characterized the changes in cytokine expression and the function of mesenchymal stromal cells (MSC) in patients with MDS, AML with myelodysplasia-related changes (MRC), a well-recognized clinical subtype of secondary AML, and de novo AML. We observed a significant inhibitory effect of MDS-MSC on T-lymphocyte proliferation and no significant differences in any of the cytokines tested. AML-MSC inhibited T-cell proliferation only at a very low MSC/T cell ratio. When compared to the control, AML-MRC-derived MSC presented a significant increase in IL6 expression, whereas de novo AML MSC presented a significant increase in the expression levels of VEGFA, CXCL12, RPGE2, IDO, IL1 beta, IL6 and IL32, followed by a decrease in IL10 expression. Furthermore, data indicate that IL-32 regulates stromal cell proliferation, has a chemotactic potential and participates in stromal cell crosstalk with leukemia cells, which could result in chemoresistance. Our results suggest that the differences between AML-MRC and de novo AML also extend into the leukemic stem cell niche and that IL-32 can participate in the regulation of the bone marrow cytokine milieu.Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)Univ Estadual Campinas, Hematol & Transfus Med Ctr, Hemoctr Unicamp, Inst Nacl Ciencia & Tecnol Sangue, Sao Paulo, BrazilUniv Sao Paulo, Ribeirao Preto Med Sch, Dept Internal Med, Sao Paulo, BrazilUniv Fed Sao Paulo, Dept Biol Sci, Sao Paulo, BrazilFed Univ Vale do Sao Francisco, Paulo Afonso, BA, BrazilUniv Fed Sao Paulo, Dept Biol Sci, Sao Paulo, BrazilWeb of Science-engNature Publishing GroupScientific ReportsDe novo AML exhibits greater microenvironment dysregulation compared to AML with myelodysplasia-related changesinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleLondon7info:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESPORIGINALWOS000391927200001.pdfapplication/pdf1765973${dspace.ui.url}/bitstream/11600/55258/1/WOS000391927200001.pdfb6b7205588523a80ea8d6873a965bd1eMD51open accessTEXTWOS000391927200001.pdf.txtWOS000391927200001.pdf.txtExtracted texttext/plain51768${dspace.ui.url}/bitstream/11600/55258/8/WOS000391927200001.pdf.txt720e9bc4806bdd19c93ef00c63a7554aMD58open accessTHUMBNAILWOS000391927200001.pdf.jpgWOS000391927200001.pdf.jpgIM Thumbnailimage/jpeg7422${dspace.ui.url}/bitstream/11600/55258/10/WOS000391927200001.pdf.jpg3e744ebe593c0b3e37cbea7b24275abfMD510open access11600/552582023-06-05 19:29:29.932open accessoai:repositorio.unifesp.br:11600/55258Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestopendoar:34652023-06-05T22:29:29Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
dc.title.en.fl_str_mv |
De novo AML exhibits greater microenvironment dysregulation compared to AML with myelodysplasia-related changes |
title |
De novo AML exhibits greater microenvironment dysregulation compared to AML with myelodysplasia-related changes |
spellingShingle |
De novo AML exhibits greater microenvironment dysregulation compared to AML with myelodysplasia-related changes Lopes, Matheus Rodrigues |
title_short |
De novo AML exhibits greater microenvironment dysregulation compared to AML with myelodysplasia-related changes |
title_full |
De novo AML exhibits greater microenvironment dysregulation compared to AML with myelodysplasia-related changes |
title_fullStr |
De novo AML exhibits greater microenvironment dysregulation compared to AML with myelodysplasia-related changes |
title_full_unstemmed |
De novo AML exhibits greater microenvironment dysregulation compared to AML with myelodysplasia-related changes |
title_sort |
De novo AML exhibits greater microenvironment dysregulation compared to AML with myelodysplasia-related changes |
author |
Lopes, Matheus Rodrigues |
author_facet |
Lopes, Matheus Rodrigues Novais Pereira, Joao Kleber Campos, Paula de Melo Machado-Neto, Joao Agostinho Traina, Fabiola Olalla Saad, Sara T. Favaro, Patricia [UNIFESP] |
author_role |
author |
author2 |
Novais Pereira, Joao Kleber Campos, Paula de Melo Machado-Neto, Joao Agostinho Traina, Fabiola Olalla Saad, Sara T. Favaro, Patricia [UNIFESP] |
author2_role |
author author author author author author |
dc.contributor.author.fl_str_mv |
Lopes, Matheus Rodrigues Novais Pereira, Joao Kleber Campos, Paula de Melo Machado-Neto, Joao Agostinho Traina, Fabiola Olalla Saad, Sara T. Favaro, Patricia [UNIFESP] |
description |
The interaction between the bone marrow microenvironment and malignant hematopoietic cells can result in the protection of leukemia cells from chemotherapy in both myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). We, herein, characterized the changes in cytokine expression and the function of mesenchymal stromal cells (MSC) in patients with MDS, AML with myelodysplasia-related changes (MRC), a well-recognized clinical subtype of secondary AML, and de novo AML. We observed a significant inhibitory effect of MDS-MSC on T-lymphocyte proliferation and no significant differences in any of the cytokines tested. AML-MSC inhibited T-cell proliferation only at a very low MSC/T cell ratio. When compared to the control, AML-MRC-derived MSC presented a significant increase in IL6 expression, whereas de novo AML MSC presented a significant increase in the expression levels of VEGFA, CXCL12, RPGE2, IDO, IL1 beta, IL6 and IL32, followed by a decrease in IL10 expression. Furthermore, data indicate that IL-32 regulates stromal cell proliferation, has a chemotactic potential and participates in stromal cell crosstalk with leukemia cells, which could result in chemoresistance. Our results suggest that the differences between AML-MRC and de novo AML also extend into the leukemic stem cell niche and that IL-32 can participate in the regulation of the bone marrow cytokine milieu. |
publishDate |
2017 |
dc.date.issued.fl_str_mv |
2017 |
dc.date.accessioned.fl_str_mv |
2020-07-17T14:03:15Z |
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2020-07-17T14:03:15Z |
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info:eu-repo/semantics/publishedVersion |
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dc.identifier.citation.fl_str_mv |
Scientific Reports. London, v. 7, p. -, 2017. |
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https://repositorio.unifesp.br/handle/11600/55258 http://dx.doi.org/10.1038/srep40707 |
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2045-2322 |
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WOS000391927200001.pdf |
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10.1038/srep40707 |
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WOS:000391927200001 |
identifier_str_mv |
Scientific Reports. London, v. 7, p. -, 2017. 2045-2322 WOS000391927200001.pdf 10.1038/srep40707 WOS:000391927200001 |
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https://repositorio.unifesp.br/handle/11600/55258 http://dx.doi.org/10.1038/srep40707 |
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