Influence of TNF and IL6 gene polymorphisms on the severity of cytopenias in Argentine patients with myelodysplastic syndromes

Autores
Bestach, Yesica Soledad; Palau Nagore, Maria Virginia; Flores, María G.; González, Jacqueline; Arbelbide, Jorge; Watman, Nora; Sieza, Yamila; Larripa, Irene Beatriz; Belli, Carolina Bárbara
Año de publicación
2017
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Myelodysplastic syndromes (MDS) represent a heterogeneous group of hematologic disorders characterized by cytopenia(s) and predisposition to leukemic progression. An immune dysregulation and an aberrant bone marrow microenvironment seem to be key elements in the physiopathological process of MDS. In order to evaluate a possible association between susceptibility and clinic-pathologic features, we genotyped 153 MDS patients for functional cytokine polymorphisms: TNF (−308 G/A), IFNG (+874 A/T and +875 CAn), IL6 (−174 G/C), and TGFB1 (+869 C/T and +915 G/C). The frequency of TNF and IL6 polymorphisms was different between patients and healthy controls (n = 131), suggesting a relatedness to MDS susceptibility in our population. Furthermore, the presence of each or both high-producing genotypes [TNF: p = 0.048, odds ratio (OR): 3.979; IL6: p = 0.001, OR: 6.835; both: p = 0.010, OR: 6.068] and thrombocytopenia at platelet counts of <50,000/μL (p = 0.004, OR: 4.857) were independently associated with an increased risk of manifesting a hemoglobin level of <8 g/dL at diagnosis. In particular, a severe bicytopenia was more frequently observed in patients with the TNF (high)_IL6 (high) combined genotype (p = 0.004, OR: 8.357), who consistently became transfusion dependent earlier (2.9 vs. 34.6 months; p = 0.001); and this likelihood was more evident in patients with lower bone marrow blast counts. The contribution of the remaining functional polymorphisms to the disease phenotype was less relevant. Our results demonstrate that TNF and IL6 gene polymorphisms, as underlying host features, are likely to play a key role in influencing the severity of the cytopenias in MDS and they may be instrumental for tailoring cytokine-target therapies.
Fil: Bestach, Yesica Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Palau Nagore, Maria Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Flores, María G.. Hospital General de Agudos “C.G. Durand”; Argentina
Fil: González, Jacqueline. Hospital General de Agudos “C.G. Durand”; Argentina
Fil: Arbelbide, Jorge. Hospital Italiano; Argentina
Fil: Watman, Nora. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; Argentina
Fil: Sieza, Yamila. Hospital Interzonal General de Agudos “Gral. San Martín”; Argentina
Fil: Larripa, Irene Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Belli, Carolina Bárbara. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Materia
CYTOPENIA
IL6
MYELODYSPLASTIC SYNDROMES
POLYMORPHISMS
TNF
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/52789
Acceder
id CONICETDig_9a33459de0e0ae6f2869e672c7dea439
oai_identifier_str oai:ri.conicet.gov.ar:11336/52789
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Influence of TNF and IL6 gene polymorphisms on the severity of cytopenias in Argentine patients with myelodysplastic syndromesBestach, Yesica SoledadPalau Nagore, Maria VirginiaFlores, María G.González, JacquelineArbelbide, JorgeWatman, NoraSieza, YamilaLarripa, Irene BeatrizBelli, Carolina BárbaraCYTOPENIAIL6MYELODYSPLASTIC SYNDROMESPOLYMORPHISMSTNFhttps://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3Myelodysplastic syndromes (MDS) represent a heterogeneous group of hematologic disorders characterized by cytopenia(s) and predisposition to leukemic progression. An immune dysregulation and an aberrant bone marrow microenvironment seem to be key elements in the physiopathological process of MDS. In order to evaluate a possible association between susceptibility and clinic-pathologic features, we genotyped 153 MDS patients for functional cytokine polymorphisms: TNF (−308 G/A), IFNG (+874 A/T and +875 CAn), IL6 (−174 G/C), and TGFB1 (+869 C/T and +915 G/C). The frequency of TNF and IL6 polymorphisms was different between patients and healthy controls (n = 131), suggesting a relatedness to MDS susceptibility in our population. Furthermore, the presence of each or both high-producing genotypes [TNF: p = 0.048, odds ratio (OR): 3.979; IL6: p = 0.001, OR: 6.835; both: p = 0.010, OR: 6.068] and thrombocytopenia at platelet counts of <50,000/μL (p = 0.004, OR: 4.857) were independently associated with an increased risk of manifesting a hemoglobin level of <8 g/dL at diagnosis. In particular, a severe bicytopenia was more frequently observed in patients with the TNF (high)_IL6 (high) combined genotype (p = 0.004, OR: 8.357), who consistently became transfusion dependent earlier (2.9 vs. 34.6 months; p = 0.001); and this likelihood was more evident in patients with lower bone marrow blast counts. The contribution of the remaining functional polymorphisms to the disease phenotype was less relevant. Our results demonstrate that TNF and IL6 gene polymorphisms, as underlying host features, are likely to play a key role in influencing the severity of the cytopenias in MDS and they may be instrumental for tailoring cytokine-target therapies.Fil: Bestach, Yesica Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Palau Nagore, Maria Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Flores, María G.. Hospital General de Agudos “C.G. Durand”; ArgentinaFil: González, Jacqueline. Hospital General de Agudos “C.G. Durand”; ArgentinaFil: Arbelbide, Jorge. Hospital Italiano; ArgentinaFil: Watman, Nora. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Sieza, Yamila. Hospital Interzonal General de Agudos “Gral. San Martín”; ArgentinaFil: Larripa, Irene Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Belli, Carolina Bárbara. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaSpringer2017-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/52789Bestach, Yesica Soledad; Palau Nagore, Maria Virginia; Flores, María G.; González, Jacqueline; Arbelbide, Jorge; et al.; Influence of TNF and IL6 gene polymorphisms on the severity of cytopenias in Argentine patients with myelodysplastic syndromes; Springer; Annals Of Hematology; 96; 8; 8-2017; 1287-12950939-5555CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1007/s00277-017-3036-4info:eu-repo/semantics/altIdentifier/url/https://link.springer.com/article/10.1007%2Fs00277-017-3036-4info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:06:31Zoai:ri.conicet.gov.ar:11336/52789instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 10:06:31.849CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Influence of TNF and IL6 gene polymorphisms on the severity of cytopenias in Argentine patients with myelodysplastic syndromes
title Influence of TNF and IL6 gene polymorphisms on the severity of cytopenias in Argentine patients with myelodysplastic syndromes
spellingShingle Influence of TNF and IL6 gene polymorphisms on the severity of cytopenias in Argentine patients with myelodysplastic syndromes
Bestach, Yesica Soledad
CYTOPENIA
IL6
MYELODYSPLASTIC SYNDROMES
POLYMORPHISMS
TNF
title_short Influence of TNF and IL6 gene polymorphisms on the severity of cytopenias in Argentine patients with myelodysplastic syndromes
title_full Influence of TNF and IL6 gene polymorphisms on the severity of cytopenias in Argentine patients with myelodysplastic syndromes
title_fullStr Influence of TNF and IL6 gene polymorphisms on the severity of cytopenias in Argentine patients with myelodysplastic syndromes
title_full_unstemmed Influence of TNF and IL6 gene polymorphisms on the severity of cytopenias in Argentine patients with myelodysplastic syndromes
title_sort Influence of TNF and IL6 gene polymorphisms on the severity of cytopenias in Argentine patients with myelodysplastic syndromes
dc.creator.none.fl_str_mv Bestach, Yesica Soledad
Palau Nagore, Maria Virginia
Flores, María G.
González, Jacqueline
Arbelbide, Jorge
Watman, Nora
Sieza, Yamila
Larripa, Irene Beatriz
Belli, Carolina Bárbara
author Bestach, Yesica Soledad
author_facet Bestach, Yesica Soledad
Palau Nagore, Maria Virginia
Flores, María G.
González, Jacqueline
Arbelbide, Jorge
Watman, Nora
Sieza, Yamila
Larripa, Irene Beatriz
Belli, Carolina Bárbara
author_role author
author2 Palau Nagore, Maria Virginia
Flores, María G.
González, Jacqueline
Arbelbide, Jorge
Watman, Nora
Sieza, Yamila
Larripa, Irene Beatriz
Belli, Carolina Bárbara
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv CYTOPENIA
IL6
MYELODYSPLASTIC SYNDROMES
POLYMORPHISMS
TNF
topic CYTOPENIA
IL6
MYELODYSPLASTIC SYNDROMES
POLYMORPHISMS
TNF
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Myelodysplastic syndromes (MDS) represent a heterogeneous group of hematologic disorders characterized by cytopenia(s) and predisposition to leukemic progression. An immune dysregulation and an aberrant bone marrow microenvironment seem to be key elements in the physiopathological process of MDS. In order to evaluate a possible association between susceptibility and clinic-pathologic features, we genotyped 153 MDS patients for functional cytokine polymorphisms: TNF (−308 G/A), IFNG (+874 A/T and +875 CAn), IL6 (−174 G/C), and TGFB1 (+869 C/T and +915 G/C). The frequency of TNF and IL6 polymorphisms was different between patients and healthy controls (n = 131), suggesting a relatedness to MDS susceptibility in our population. Furthermore, the presence of each or both high-producing genotypes [TNF: p = 0.048, odds ratio (OR): 3.979; IL6: p = 0.001, OR: 6.835; both: p = 0.010, OR: 6.068] and thrombocytopenia at platelet counts of <50,000/μL (p = 0.004, OR: 4.857) were independently associated with an increased risk of manifesting a hemoglobin level of <8 g/dL at diagnosis. In particular, a severe bicytopenia was more frequently observed in patients with the TNF (high)_IL6 (high) combined genotype (p = 0.004, OR: 8.357), who consistently became transfusion dependent earlier (2.9 vs. 34.6 months; p = 0.001); and this likelihood was more evident in patients with lower bone marrow blast counts. The contribution of the remaining functional polymorphisms to the disease phenotype was less relevant. Our results demonstrate that TNF and IL6 gene polymorphisms, as underlying host features, are likely to play a key role in influencing the severity of the cytopenias in MDS and they may be instrumental for tailoring cytokine-target therapies.
Fil: Bestach, Yesica Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Palau Nagore, Maria Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Flores, María G.. Hospital General de Agudos “C.G. Durand”; Argentina
Fil: González, Jacqueline. Hospital General de Agudos “C.G. Durand”; Argentina
Fil: Arbelbide, Jorge. Hospital Italiano; Argentina
Fil: Watman, Nora. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; Argentina
Fil: Sieza, Yamila. Hospital Interzonal General de Agudos “Gral. San Martín”; Argentina
Fil: Larripa, Irene Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Belli, Carolina Bárbara. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
description Myelodysplastic syndromes (MDS) represent a heterogeneous group of hematologic disorders characterized by cytopenia(s) and predisposition to leukemic progression. An immune dysregulation and an aberrant bone marrow microenvironment seem to be key elements in the physiopathological process of MDS. In order to evaluate a possible association between susceptibility and clinic-pathologic features, we genotyped 153 MDS patients for functional cytokine polymorphisms: TNF (−308 G/A), IFNG (+874 A/T and +875 CAn), IL6 (−174 G/C), and TGFB1 (+869 C/T and +915 G/C). The frequency of TNF and IL6 polymorphisms was different between patients and healthy controls (n = 131), suggesting a relatedness to MDS susceptibility in our population. Furthermore, the presence of each or both high-producing genotypes [TNF: p = 0.048, odds ratio (OR): 3.979; IL6: p = 0.001, OR: 6.835; both: p = 0.010, OR: 6.068] and thrombocytopenia at platelet counts of <50,000/μL (p = 0.004, OR: 4.857) were independently associated with an increased risk of manifesting a hemoglobin level of <8 g/dL at diagnosis. In particular, a severe bicytopenia was more frequently observed in patients with the TNF (high)_IL6 (high) combined genotype (p = 0.004, OR: 8.357), who consistently became transfusion dependent earlier (2.9 vs. 34.6 months; p = 0.001); and this likelihood was more evident in patients with lower bone marrow blast counts. The contribution of the remaining functional polymorphisms to the disease phenotype was less relevant. Our results demonstrate that TNF and IL6 gene polymorphisms, as underlying host features, are likely to play a key role in influencing the severity of the cytopenias in MDS and they may be instrumental for tailoring cytokine-target therapies.
publishDate 2017
dc.date.none.fl_str_mv 2017-08
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/52789
Bestach, Yesica Soledad; Palau Nagore, Maria Virginia; Flores, María G.; González, Jacqueline; Arbelbide, Jorge; et al.; Influence of TNF and IL6 gene polymorphisms on the severity of cytopenias in Argentine patients with myelodysplastic syndromes; Springer; Annals Of Hematology; 96; 8; 8-2017; 1287-1295
0939-5555
CONICET Digital
CONICET
url http://hdl.handle.net/11336/52789
identifier_str_mv Bestach, Yesica Soledad; Palau Nagore, Maria Virginia; Flores, María G.; González, Jacqueline; Arbelbide, Jorge; et al.; Influence of TNF and IL6 gene polymorphisms on the severity of cytopenias in Argentine patients with myelodysplastic syndromes; Springer; Annals Of Hematology; 96; 8; 8-2017; 1287-1295
0939-5555
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1007/s00277-017-3036-4
info:eu-repo/semantics/altIdentifier/url/https://link.springer.com/article/10.1007%2Fs00277-017-3036-4
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Springer
publisher.none.fl_str_mv Springer
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1842269962174988288
score 13.13397

Publicaciones similares