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The Genotype of the Donor for the (GT)n Polymorphism in the Promoter/Enhancer of FOXP3 Is Associated with the Development of Severe Acute GVHD but Does Not Affect the GVL Effect after Myeloablative HLA-Identical Allogeneic Stem Cell Transplantation

Authors :
Víctor Noriega
Carolina Martínez-Laperche
Elena Buces
Marjorie Pion
Noemí Sánchez-Hernández
Beatriz Martín-Antonio
Vicent Guillem
Anna Bosch-Vizcaya
Leyre Bento
Milagros González-Rivera
Pascual Balsalobre
Mi Kwon
David Serrano
Jorge Gayoso
Rafael de la Cámara
Salut Brunet
Rafael Rojas-Contreras
José B Nieto
Carmen Martínez
Marcos Gónzalez
Ildefonso Espigado
Juan C Vallejo
Antonia Sampol
Antonio Jiménez-Velasco
Alvaro Urbano-Ispizua
Carlos Solano
David Gallardo
José L Díez-Martín
Ismael Buño
Spanish Hematopoietic Stem Cell Transplantation and Cell Therapy Group (GETH)
Universitat de Barcelona
Spanish Hematopoietic Stem Cell Transplantario and Cell Therapy Group (GETH)
[Noriega,V
Martínez-Laperche,C
Buces,E
Sánchez-Hernández,N
Bento,L
Balsalobre,P
Kwon,M
Serrano,D
Gayoso,J
Díez-Martín,JL
Buño,I] Department of Hematology, Hospital General Universitario Gregorio Marañón, Madrid, Spain. [Noriega,V
Pion,M
González-Rivera,M
Buño,I] Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain. [Pion,M] Department of Inmunology, Hospital General Universitario Gregorio Marañón, Madrid, Spain. [Martín-Antonio,B
Urbano-Ispizua,A] Department of Hematology, Hospital Clinic, University of Barcelona, IDIBAPS, Instituto de Investigación Josep Carreras (IJC), Barcelona, Spain. [Guillem,V
Solano,C] Department of Hematology and Medical Oncology, Hospital Clínico Universitario de Valencia, Universitat de Valencia, Instituto de Investigación Sanitaria INCLIVA, Valencia, Spain. [Bosch-Vizcaya,A
Gallardo,D] Department of Hematology, ICO Girona, Hospital Josep Trueta, IDIBGI Foundation, Girona, Spain. [González-Rivera,M] DNA Sequencing Core Facility, Hospital General Universitario Gregorio Marañón, Madrid, Spain. [de la Cámara,R] Department of Hematology, Hospital La Princesa, Madrid, Spain. [Brunet,S] Department of Clinical Hematology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. [Rojas-Contreras,R] Department of Hematology, Hospital Reina Sofia, Cordoba, Spain. [Nieto,JB] Department of Hematology, Hospital Morales Meseguer, Murcia, Spain. [Martínez,C] Department of Hematology, Hospital Clínic, Barcelona, Spain. [González,M] Department of Hematology, University Hospital of Salamanca, Salamanca, Spain. [Espigado,I] Department of Hematology and Hemotherapy, Hospital Universitario Virgen del Rocío, Seville, Spain. [Vallejo,JC] Department of Hematology, Hospital Universitario Central de Asturias, Oviedo, Spain. [Sampol,A] Department of Hematology, Hospital Universitario Son Espases, Palma de Mallorca, Islas Baleares, Spain. [Jiménez-Velasco,A] Department of Hematology, Hospital Regional Universitario de Málaga, Málaga, Spain.
This work was partially supported by the Ministry of Economy and Competitiveness ISCIII-FIS grants PI08/1463, PI11/00708, PI14-01731 and RD12/0036/0061, co-financed by ERDF (FEDER) Funds from the European Commission, the Fundación LAIR and Asociación Madrileña de Hematología y Hemoterapia (AMHH). ISCIII-FIS grants PI01-3624, PI08- 36173 and The Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM).
Source :
PLoS ONE, Vol 10, Iss 10, p e0140454 (2015), Recercat. Dipósit de la Recerca de Catalunya, instname, PLoS ONE, Repositorio Institucional de la Consejería de Sanidad de la Comunidad de Madrid, Consejería de Sanidad de la Comunidad de Madrid, Dipòsit Digital de la UB, Universidad de Barcelona, PLoS One, r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
Publication Year :
2015
Publisher :
Public Library of Science (PLoS), 2015.

Abstract

The FOXP3 gene encodes for a protein (Foxp3) involved in the development and functional activity of regulatory T cells (CD4+/CD25+/Foxp3+), which exert regulatory and suppressive roles over the immune system. After allogeneic stem cell transplantation, regulatory T cells are known to mitigate graft versus host disease while probably maintaining a graft versus leukemia effect. Short alleles (<br />This work was partially supported by the Ministry of Economy and Competitiveness ISCIII-FIS grants PI08/1463, PI11/00708, PI14-01731 and RD12/0036/0061, co-financed by ERDF (FEDER) Funds from the European Commission, as well as grants from the Fundacion LAIR and Asociacion Madrilena de Hematologia y Hemoterapia (AMHH). Sequencer 3130xl Genetic Analyzer was partially supported by ISCIII-FIS grants PI01-3624, PI08-36173. VN and CML were partially supported by a Post-Residency Research Fellowship from the Instituto de Investigacion Sanitaria Gregorio Maranon (IiSGM).

Subjects

Subjects :
Male
Análisis de supervivencia
trasplante de células madre hematopoyéticas
medicine.medical_treatment
humanos
Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Survival Analysis [Medical Subject Headings]
Graft vs Host Disease
lcsh:Medicine
Polimorfismo genético
Named Groups::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings]
Hematopoietic stem cell transplantation
Stem cells
Regiones promotoras genéticas
Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Genetic Association Studies [Medical Subject Headings]
Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings]
Trasplante homólogo
IL-2 receptor
Lymphocytes
Masculino
Promoter Regions, Genetic
lcsh:Science
mediana edad
anciano
Multidisciplinary
Adulto
Femenino
Analytical, Diagnostic and Therapeutic Techniques and Equipment::Surgical Procedures, Operative::Transplantation::Cell Transplantation::Stem Cell Transplantation::Hematopoietic Stem Cell Transplantation [Medical Subject Headings]
Hematopoietic Stem Cell Transplantation
FOXP3
Forkhead Transcription Factors
adulto
análisis de supervivencia
Middle Aged
Tissue Donors
Humanos
estudios de asociación genética
adulto joven
medicine.anatomical_structure
surgical procedures, operative
Cèl·lules T
Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Transcription Factors::Winged-Helix Transcription Factors::Forkhead Transcription Factors [Medical Subject Headings]
Female
Phenomena and Processes::Genetic Phenomena::Genotype [Medical Subject Headings]
Factores de transcripción en cabeza de tenedor
Cèl·lules mare
Trasplante de células madre hematopoyéticas
Research Article
Adult
Named Groups::Persons::Age Groups::Adult::Young Adult [Medical Subject Headings]
Genotype
Graft-vs-Leukemia Effect
Regulatory T cell
Anciano
T cells
Check Tags::Male [Medical Subject Headings]
Graft vs Leukemia Effect
factores de transcripción en cabeza de tenedor
Human leukocyte antigen
Biology
Enfermedad injerto contra huésped
Limfòcits
Young Adult
Donantes de tejidos
Named Groups::Persons::Tissue Donors [Medical Subject Headings]
Named Groups::Persons::Age Groups::Adult [Medical Subject Headings]
medicine
Humans
Transplantation, Homologous
Named Groups::Persons::Age Groups::Adult::Aged [Medical Subject Headings]
Genetic Association Studies
Aged
Mediana edad
Transplantation
Polymorphism, Genetic
Estudios de asociación genética
Efecto injerto contra leucemia
lcsh:R
donantes de tejidos
trasplante
Phenomena and Processes::Genetic Phenomena::Genetic Variation::Polymorphism, Genetic [Medical Subject Headings]
medicine.disease
Survival Analysis
Diseases::Immune System Diseases::Graft vs Host Disease [Medical Subject Headings]
Analytical, Diagnostic and Therapeutic Techniques and Equipment::Surgical Procedures, Operative::Transplantation::Transplantation, Homologous [Medical Subject Headings]
efecto injerto contra leucemia
Graft-versus-host disease
Check Tags::Female [Medical Subject Headings]
Immunology
Phenomena and Processes::Immune System Phenomena::Immune System Processes::Transplantation Immunology::Graft vs Host Reaction::Graft vs Tumor Effect::Graft vs Leukemia Effect [Medical Subject Headings]
enfermedad injerto contra huésped
Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Genes::Gene Components::Regulatory Elements, Transcriptional::Promoter Regions, Genetic [Medical Subject Headings]
lcsh:Q
genotipo
Genotipo

Details

Language :
English
ISSN :
19326203
Volume :
10
Issue :
10
Database :
OpenAIRE
Journal :
PLoS ONE
Accession number :
edsair.doi.dedup.....726ef6b79f335bf9a294addd7a43ffab