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Serotonin receptor type 1B constitutes a therapeutic target for MDS and CMML

Myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML) are chronic myeloid clonal neoplasms. To date, the only potentially curative therapy for these disorders remains allogeneic hematopoietic progenitor cell transplantation (HCT), although patient eligibility is limited due to h...

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Autores principales: Banús-Mulet, Antònia, Etxabe, Amaia, Cornet-Masana, Josep Maria, Torrente, Miguel Ángel, Lara-Castillo, María Carmen, Palomo, Laura, Nomdedeu, Meritxell, Díaz-Beyá, Marina, Solé, Francesc, Nomdedeu, Benet, Esteve, Jordi, Risueño, Ruth M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6141614/
https://www.ncbi.nlm.nih.gov/pubmed/30224768
http://dx.doi.org/10.1038/s41598-018-32306-4
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author Banús-Mulet, Antònia
Etxabe, Amaia
Cornet-Masana, Josep Maria
Torrente, Miguel Ángel
Lara-Castillo, María Carmen
Palomo, Laura
Nomdedeu, Meritxell
Díaz-Beyá, Marina
Solé, Francesc
Nomdedeu, Benet
Esteve, Jordi
Risueño, Ruth M.
author_facet Banús-Mulet, Antònia
Etxabe, Amaia
Cornet-Masana, Josep Maria
Torrente, Miguel Ángel
Lara-Castillo, María Carmen
Palomo, Laura
Nomdedeu, Meritxell
Díaz-Beyá, Marina
Solé, Francesc
Nomdedeu, Benet
Esteve, Jordi
Risueño, Ruth M.
author_sort Banús-Mulet, Antònia
collection PubMed
description Myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML) are chronic myeloid clonal neoplasms. To date, the only potentially curative therapy for these disorders remains allogeneic hematopoietic progenitor cell transplantation (HCT), although patient eligibility is limited due to high morbimortality associated with this procedure coupled with advanced age of most patients. Dopamine receptors (DRs) and serotonin receptors type 1 (HTR1s) were identified as cancer stem cell therapeutic targets in acute myeloid leukemia. Given their close pathophysiologic relationship, expression of HTR1s and DRs was interrogated in MDS and CMML. Both receptors were differentially expressed in patient samples compared to healthy donors. Treatment with HTR1B antagonists reduced cell viability. HTR1 antagonists showed a synergistic cytotoxic effect with currently approved hypomethylating agents in AML cells. Our results suggest that HTR1B constitutes a novel therapeutic target for MDS and CMML. Due to its druggability, the clinical development of new regimens based on this target is promising.
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spelling pubmed-61416142018-09-20 Serotonin receptor type 1B constitutes a therapeutic target for MDS and CMML Banús-Mulet, Antònia Etxabe, Amaia Cornet-Masana, Josep Maria Torrente, Miguel Ángel Lara-Castillo, María Carmen Palomo, Laura Nomdedeu, Meritxell Díaz-Beyá, Marina Solé, Francesc Nomdedeu, Benet Esteve, Jordi Risueño, Ruth M. Sci Rep Article Myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML) are chronic myeloid clonal neoplasms. To date, the only potentially curative therapy for these disorders remains allogeneic hematopoietic progenitor cell transplantation (HCT), although patient eligibility is limited due to high morbimortality associated with this procedure coupled with advanced age of most patients. Dopamine receptors (DRs) and serotonin receptors type 1 (HTR1s) were identified as cancer stem cell therapeutic targets in acute myeloid leukemia. Given their close pathophysiologic relationship, expression of HTR1s and DRs was interrogated in MDS and CMML. Both receptors were differentially expressed in patient samples compared to healthy donors. Treatment with HTR1B antagonists reduced cell viability. HTR1 antagonists showed a synergistic cytotoxic effect with currently approved hypomethylating agents in AML cells. Our results suggest that HTR1B constitutes a novel therapeutic target for MDS and CMML. Due to its druggability, the clinical development of new regimens based on this target is promising. Nature Publishing Group UK 2018-09-17 /pmc/articles/PMC6141614/ /pubmed/30224768 http://dx.doi.org/10.1038/s41598-018-32306-4 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Banús-Mulet, Antònia
Etxabe, Amaia
Cornet-Masana, Josep Maria
Torrente, Miguel Ángel
Lara-Castillo, María Carmen
Palomo, Laura
Nomdedeu, Meritxell
Díaz-Beyá, Marina
Solé, Francesc
Nomdedeu, Benet
Esteve, Jordi
Risueño, Ruth M.
Serotonin receptor type 1B constitutes a therapeutic target for MDS and CMML
title Serotonin receptor type 1B constitutes a therapeutic target for MDS and CMML
title_full Serotonin receptor type 1B constitutes a therapeutic target for MDS and CMML
title_fullStr Serotonin receptor type 1B constitutes a therapeutic target for MDS and CMML
title_full_unstemmed Serotonin receptor type 1B constitutes a therapeutic target for MDS and CMML
title_short Serotonin receptor type 1B constitutes a therapeutic target for MDS and CMML
title_sort serotonin receptor type 1b constitutes a therapeutic target for mds and cmml
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6141614/
https://www.ncbi.nlm.nih.gov/pubmed/30224768
http://dx.doi.org/10.1038/s41598-018-32306-4
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