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Bone Marrow Mast Cell Antibody-Targetable Cell Surface Protein Expression Profiles in Systemic Mastocytosis

Despite recent therapeutic advances, systemic mastocytosis (SM) remains an incurable disease due to limited complete remission (CR) rates even after novel therapies. To date, no study has evaluated the expression on SM bone marrow mast cells (BMMC) of large panel of cell surface suitable for antibod...

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Autores principales: Dasilva-Freire, Noelia, Mayado, Andrea, Teodosio, Cristina, Jara-Acevedo, María, Álvarez-Twose, Iván, Matito, Almudena, Sánchez-Muñoz, Laura, Caldas, Carolina, Henriques, Ana, Muñoz-González, Javier I., García-Montero, Andrés C., Sánchez-Gallego, J. Ignacio, Escribano, Luis, Orfao, Alberto
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6387409/
https://www.ncbi.nlm.nih.gov/pubmed/30696068
http://dx.doi.org/10.3390/ijms20030552
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author Dasilva-Freire, Noelia
Mayado, Andrea
Teodosio, Cristina
Jara-Acevedo, María
Álvarez-Twose, Iván
Matito, Almudena
Sánchez-Muñoz, Laura
Caldas, Carolina
Henriques, Ana
Muñoz-González, Javier I.
García-Montero, Andrés C.
Sánchez-Gallego, J. Ignacio
Escribano, Luis
Orfao, Alberto
author_facet Dasilva-Freire, Noelia
Mayado, Andrea
Teodosio, Cristina
Jara-Acevedo, María
Álvarez-Twose, Iván
Matito, Almudena
Sánchez-Muñoz, Laura
Caldas, Carolina
Henriques, Ana
Muñoz-González, Javier I.
García-Montero, Andrés C.
Sánchez-Gallego, J. Ignacio
Escribano, Luis
Orfao, Alberto
author_sort Dasilva-Freire, Noelia
collection PubMed
description Despite recent therapeutic advances, systemic mastocytosis (SM) remains an incurable disease due to limited complete remission (CR) rates even after novel therapies. To date, no study has evaluated the expression on SM bone marrow mast cells (BMMC) of large panel of cell surface suitable for antibody-targeted therapy. In this study, we analyzed the expression profile of six cell-surface proteins for which antibody-based therapies are available, on BMMC from 166 SM patients vs. 40 controls. Overall, variable patterns of expression for the markers evaluated were observed among SM BMMC. Thus, CD22, CD30, and CD123, while expressed on BMMC from patients within every subtype of SM, showed highly variable patterns with a significant fraction of negative cases among advanced SM (aggressive SM (ASM), ASM with an associated clonal non-MC lineage disease (ASM-AHN) and MC leukemia (MCL)), 36%, 46%, and 39%, respectively. In turn, CD25 and FcεRI were found to be expressed in most cases (89% and 92%) in virtually all BMMC (median: 92% and 95%) from both indolent and advanced SM, but with lower/absent levels in a significant fraction of MC leukemia (MCL) and both in MCL and well-differentiated SM (WDSM) patients, respectively. In contrast, CD33 was the only marker expressed on all BMMC from every SM patient. Thus, CD33 emerges as the best potentially targetable cell-surface membrane marker in SM, particularly in advanced SM.
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spelling pubmed-63874092019-02-27 Bone Marrow Mast Cell Antibody-Targetable Cell Surface Protein Expression Profiles in Systemic Mastocytosis Dasilva-Freire, Noelia Mayado, Andrea Teodosio, Cristina Jara-Acevedo, María Álvarez-Twose, Iván Matito, Almudena Sánchez-Muñoz, Laura Caldas, Carolina Henriques, Ana Muñoz-González, Javier I. García-Montero, Andrés C. Sánchez-Gallego, J. Ignacio Escribano, Luis Orfao, Alberto Int J Mol Sci Article Despite recent therapeutic advances, systemic mastocytosis (SM) remains an incurable disease due to limited complete remission (CR) rates even after novel therapies. To date, no study has evaluated the expression on SM bone marrow mast cells (BMMC) of large panel of cell surface suitable for antibody-targeted therapy. In this study, we analyzed the expression profile of six cell-surface proteins for which antibody-based therapies are available, on BMMC from 166 SM patients vs. 40 controls. Overall, variable patterns of expression for the markers evaluated were observed among SM BMMC. Thus, CD22, CD30, and CD123, while expressed on BMMC from patients within every subtype of SM, showed highly variable patterns with a significant fraction of negative cases among advanced SM (aggressive SM (ASM), ASM with an associated clonal non-MC lineage disease (ASM-AHN) and MC leukemia (MCL)), 36%, 46%, and 39%, respectively. In turn, CD25 and FcεRI were found to be expressed in most cases (89% and 92%) in virtually all BMMC (median: 92% and 95%) from both indolent and advanced SM, but with lower/absent levels in a significant fraction of MC leukemia (MCL) and both in MCL and well-differentiated SM (WDSM) patients, respectively. In contrast, CD33 was the only marker expressed on all BMMC from every SM patient. Thus, CD33 emerges as the best potentially targetable cell-surface membrane marker in SM, particularly in advanced SM. MDPI 2019-01-28 /pmc/articles/PMC6387409/ /pubmed/30696068 http://dx.doi.org/10.3390/ijms20030552 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Dasilva-Freire, Noelia
Mayado, Andrea
Teodosio, Cristina
Jara-Acevedo, María
Álvarez-Twose, Iván
Matito, Almudena
Sánchez-Muñoz, Laura
Caldas, Carolina
Henriques, Ana
Muñoz-González, Javier I.
García-Montero, Andrés C.
Sánchez-Gallego, J. Ignacio
Escribano, Luis
Orfao, Alberto
Bone Marrow Mast Cell Antibody-Targetable Cell Surface Protein Expression Profiles in Systemic Mastocytosis
title Bone Marrow Mast Cell Antibody-Targetable Cell Surface Protein Expression Profiles in Systemic Mastocytosis
title_full Bone Marrow Mast Cell Antibody-Targetable Cell Surface Protein Expression Profiles in Systemic Mastocytosis
title_fullStr Bone Marrow Mast Cell Antibody-Targetable Cell Surface Protein Expression Profiles in Systemic Mastocytosis
title_full_unstemmed Bone Marrow Mast Cell Antibody-Targetable Cell Surface Protein Expression Profiles in Systemic Mastocytosis
title_short Bone Marrow Mast Cell Antibody-Targetable Cell Surface Protein Expression Profiles in Systemic Mastocytosis
title_sort bone marrow mast cell antibody-targetable cell surface protein expression profiles in systemic mastocytosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6387409/
https://www.ncbi.nlm.nih.gov/pubmed/30696068
http://dx.doi.org/10.3390/ijms20030552
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