Expressão da tetraspanina (CD81) em mieloblastos e sua associação com o perfil de citocinas Th2 e prognóstico adverso em leucemia mielóide aguda

Detalhes bibliográficos
Autor(a) principal: SOARES, Rossy-Eric Pereira
Data de Publicação: 2021
Tipo de documento: Tese
Idioma: por
Título da fonte: Biblioteca Digital de Teses e Dissertações da UFMA
Texto Completo: https://tedebc.ufma.br/jspui/handle/tede/tede/4395
Resumo: CD81, a member of the testraspanin family, is a membrane protein involved in immunosuppressive responses and associated with adverse outcomes in multiple myeloma and acute myoid leukemia (AML). Although studies support the occurrence of dysregulation in the production of cytokines in hematologic malignancies, the relationship between the expression of CD81 in myeloblasts and the cytokine profile in patients with AML is not known. Thus, we evaluated the association between CD81 expression and Th1, Th2 and Th17 cytokine levels, as well as its prognostic value in AML. For this, 121 patients diagnosed with AML and 40 control subjects were studied. We observed the expression of CD81 in 100/121 (82.6%) patients (P<0.05). Serum levels of IL-2, IL-4, IL-10, TNFα and IFNγ were significantly higher in AML patients compared to the control group (P<0.05). The expression of CD81, associated with low levels of IL 2 and IFNγ and high levels of IL-4 and IL-10, negatively affected overall survival, event free survival and contributed to early relapse. Furthermore, we demonstrated, through principal component analysis, that there is a segregation between groups with the lowest and highest percentage of blasts expressing CD81 (P<0.05) for IL-2, IL-10, IFNγ and overall survival. In summary, we confirm that CD81 is a poor prognostic marker for AML, possibly because its expression present in a higher frequency of blasts is associated with an immunosuppressive immune response profile. Furthermore, we demonstrated that this tetraspanin is capable of separating risk groups not only due to the presence or absence of expression, but mainly due to the frequency with which the blasts present expression of this antigen. Finally, our findings contribute to the understanding of the relationship of CD81 expression with the immune response in patients with AML and to expand investigations into the role of this tetraspania in this neoplasm, in addition, of course, highlighting it as a useful marker to predict prognosis and possibly, candidate for target therapy.
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spelling PEREIRA, Silma Regina Ferreirahttp://lattes.cnpq.br/8510523766431676PEREIRA, Silma Regina Ferreirahttp://lattes.cnpq.br/8510523766431676BIRBRAIR, Alexanderhttp://lattes.cnpq.br/5401157008587054BURBANO, Rommel Mario Rodriguezhttp://lattes.cnpq.br/4362051219348099PEREIRA, Eduardo Martins de Sousattp://lattes.cnpq.br/4448263553675550SANTOS, Ana Paula Azevedo doshttp://lattes.cnpq.br/1484034198638245http://lattes.cnpq.br/3818830250131344SOARES, Rossy-Eric Pereira2022-12-06T17:39:16Z2021-07-01SOARES, Rossy-Eric Pereira. Expressão da tetraspanina (CD81) em mieloblastos e sua associação com o perfil de citocinas Th2 e prognóstico adverso em leucemia mielóide aguda. 2021.129 f. Tese (Programa de Pós-Graduação em Ciências da Saúde/CCBS) - Universidade Federal do Maranhão, São Luís, 2021https://tedebc.ufma.br/jspui/handle/tede/tede/4395CD81, a member of the testraspanin family, is a membrane protein involved in immunosuppressive responses and associated with adverse outcomes in multiple myeloma and acute myoid leukemia (AML). Although studies support the occurrence of dysregulation in the production of cytokines in hematologic malignancies, the relationship between the expression of CD81 in myeloblasts and the cytokine profile in patients with AML is not known. Thus, we evaluated the association between CD81 expression and Th1, Th2 and Th17 cytokine levels, as well as its prognostic value in AML. For this, 121 patients diagnosed with AML and 40 control subjects were studied. We observed the expression of CD81 in 100/121 (82.6%) patients (P<0.05). Serum levels of IL-2, IL-4, IL-10, TNFα and IFNγ were significantly higher in AML patients compared to the control group (P<0.05). The expression of CD81, associated with low levels of IL 2 and IFNγ and high levels of IL-4 and IL-10, negatively affected overall survival, event free survival and contributed to early relapse. Furthermore, we demonstrated, through principal component analysis, that there is a segregation between groups with the lowest and highest percentage of blasts expressing CD81 (P<0.05) for IL-2, IL-10, IFNγ and overall survival. In summary, we confirm that CD81 is a poor prognostic marker for AML, possibly because its expression present in a higher frequency of blasts is associated with an immunosuppressive immune response profile. Furthermore, we demonstrated that this tetraspanin is capable of separating risk groups not only due to the presence or absence of expression, but mainly due to the frequency with which the blasts present expression of this antigen. Finally, our findings contribute to the understanding of the relationship of CD81 expression with the immune response in patients with AML and to expand investigations into the role of this tetraspania in this neoplasm, in addition, of course, highlighting it as a useful marker to predict prognosis and possibly, candidate for target therapy.CD81, membro da família das testraspaninas, é uma proteína de membrana relacionada à respostas imunossupressoras e está associada a prognósticos adversos em mieloma múltiplo e leucemia mieóide aguda (LMA). Embora estudos apoiem a ocorrência de desregulação na produção de citocinas nas neoplasias hematológicas, não é conhecida a relação entre a expressão de CD81 em mieloblastos e o perfil de citocinas em pacientes com LMA. Assim, avaliamos a associação entre a expressão de CD81 e os níveis de citocinas Th1, Th2 e Th17, e seu valor prognóstico em LMA. Para isso, foram estudados 121 pacientes diagnosticados com LMA e 40 indivíduos controle. Observamos a expressão de CD81 em 100/121 (82,6%) pacientes (P<0,05). Os níveis séricos de IL-2, IL-4, IL-10, TNFα e IFNγ foram significativamente mais elevados nos pacientes com LMA em relação ao grupo controle (P<0,05). Observamos também que os níveis de IL-2 e IFNγ foram menores nos pacientes com maior percentual de blastos positivos para CD81, enquanto os níveis séricos de IL-4 e IL-10 foram superiores (P<0,05). A expressão de CD81, associada aos baixos níveis de IL-2 e IFNγ e altos níveis de IL-4 e IL-10, afetou negativamente a sobrevida global, sobrevida livre de eventos e contribuiu para recidiva precoce. Além disso, demonstramos, através da análise do componente principal, que há segregação entre os grupos com menor e maior percentual de blastos que expressavam CD81 (P<0,05) para IL-2, IL-10, IFNγ e sobrevida global. Em suma, ratificamos que CD81 é um marcador de mau prognóstico para LMA, e sugerimos que esse prognóstico adverso está associado a um perfil de resposta imunossupressora. Além disso, demonstramos que esta tetraspanina é capaz de separar grupos de risco não somente pela presença ou ausência de expressão, mas, principalmente, pela frequência com que os blastos apresentam expressão deste antígeno. Por fim, nossos achados contribuem para compreensão da relação da expressão de CD81 com a resposta imune nos pacientes com LMA e amplia o conhecimento sobre o papel desta tetraspania na LMA, além, claro, de evidenciá-la como marcador útil para prever prognóstico e, possivelmente, candidato à terapia alvo.Submitted by Daniella Santos (daniella.santos@ufma.br) on 2022-12-06T17:39:16Z No. of bitstreams: 1 Rossy-Eric.pdf: 311783 bytes, checksum: 877cdb39fc1f67e1f47d2438da1cea31 (MD5)Made available in DSpace on 2022-12-06T17:39:16Z (GMT). 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dc.title.por.fl_str_mv Expressão da tetraspanina (CD81) em mieloblastos e sua associação com o perfil de citocinas Th2 e prognóstico adverso em leucemia mielóide aguda
dc.title.alternative.eng.fl_str_mv Tetraspanin (CD81) expression in myeloblasts and its association with the Th2 cytokine profile and adverse prognosis in acute myelogenous leukemia
title Expressão da tetraspanina (CD81) em mieloblastos e sua associação com o perfil de citocinas Th2 e prognóstico adverso em leucemia mielóide aguda
spellingShingle Expressão da tetraspanina (CD81) em mieloblastos e sua associação com o perfil de citocinas Th2 e prognóstico adverso em leucemia mielóide aguda
SOARES, Rossy-Eric Pereira
CD81;
LMA;
citocinas;
CD81;
AML.
CD81,
AML,
cytokines,
prognosis.
Ciências da Saúde
title_short Expressão da tetraspanina (CD81) em mieloblastos e sua associação com o perfil de citocinas Th2 e prognóstico adverso em leucemia mielóide aguda
title_full Expressão da tetraspanina (CD81) em mieloblastos e sua associação com o perfil de citocinas Th2 e prognóstico adverso em leucemia mielóide aguda
title_fullStr Expressão da tetraspanina (CD81) em mieloblastos e sua associação com o perfil de citocinas Th2 e prognóstico adverso em leucemia mielóide aguda
title_full_unstemmed Expressão da tetraspanina (CD81) em mieloblastos e sua associação com o perfil de citocinas Th2 e prognóstico adverso em leucemia mielóide aguda
title_sort Expressão da tetraspanina (CD81) em mieloblastos e sua associação com o perfil de citocinas Th2 e prognóstico adverso em leucemia mielóide aguda
author SOARES, Rossy-Eric Pereira
author_facet SOARES, Rossy-Eric Pereira
author_role author
dc.contributor.advisor1.fl_str_mv PEREIRA, Silma Regina Ferreira
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/8510523766431676
dc.contributor.referee1.fl_str_mv PEREIRA, Silma Regina Ferreira
dc.contributor.referee1Lattes.fl_str_mv http://lattes.cnpq.br/8510523766431676
dc.contributor.referee2.fl_str_mv BIRBRAIR, Alexander
dc.contributor.referee2Lattes.fl_str_mv http://lattes.cnpq.br/5401157008587054
dc.contributor.referee3.fl_str_mv BURBANO, Rommel Mario Rodriguez
dc.contributor.referee3Lattes.fl_str_mv http://lattes.cnpq.br/4362051219348099
dc.contributor.referee4.fl_str_mv PEREIRA, Eduardo Martins de Sousa
dc.contributor.referee4Lattes.fl_str_mv ttp://lattes.cnpq.br/4448263553675550
dc.contributor.referee5.fl_str_mv SANTOS, Ana Paula Azevedo dos
dc.contributor.referee5Lattes.fl_str_mv http://lattes.cnpq.br/1484034198638245
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/3818830250131344
dc.contributor.author.fl_str_mv SOARES, Rossy-Eric Pereira
contributor_str_mv PEREIRA, Silma Regina Ferreira
PEREIRA, Silma Regina Ferreira
BIRBRAIR, Alexander
BURBANO, Rommel Mario Rodriguez
PEREIRA, Eduardo Martins de Sousa
SANTOS, Ana Paula Azevedo dos
dc.subject.por.fl_str_mv CD81;
LMA;
topic CD81;
LMA;
citocinas;
CD81;
AML.
CD81,
AML,
cytokines,
prognosis.
Ciências da Saúde
dc.subject.eng.fl_str_mv citocinas;
CD81;
AML.
CD81,
AML,
cytokines,
prognosis.
dc.subject.cnpq.fl_str_mv Ciências da Saúde
description CD81, a member of the testraspanin family, is a membrane protein involved in immunosuppressive responses and associated with adverse outcomes in multiple myeloma and acute myoid leukemia (AML). Although studies support the occurrence of dysregulation in the production of cytokines in hematologic malignancies, the relationship between the expression of CD81 in myeloblasts and the cytokine profile in patients with AML is not known. Thus, we evaluated the association between CD81 expression and Th1, Th2 and Th17 cytokine levels, as well as its prognostic value in AML. For this, 121 patients diagnosed with AML and 40 control subjects were studied. We observed the expression of CD81 in 100/121 (82.6%) patients (P<0.05). Serum levels of IL-2, IL-4, IL-10, TNFα and IFNγ were significantly higher in AML patients compared to the control group (P<0.05). The expression of CD81, associated with low levels of IL 2 and IFNγ and high levels of IL-4 and IL-10, negatively affected overall survival, event free survival and contributed to early relapse. Furthermore, we demonstrated, through principal component analysis, that there is a segregation between groups with the lowest and highest percentage of blasts expressing CD81 (P<0.05) for IL-2, IL-10, IFNγ and overall survival. In summary, we confirm that CD81 is a poor prognostic marker for AML, possibly because its expression present in a higher frequency of blasts is associated with an immunosuppressive immune response profile. Furthermore, we demonstrated that this tetraspanin is capable of separating risk groups not only due to the presence or absence of expression, but mainly due to the frequency with which the blasts present expression of this antigen. Finally, our findings contribute to the understanding of the relationship of CD81 expression with the immune response in patients with AML and to expand investigations into the role of this tetraspania in this neoplasm, in addition, of course, highlighting it as a useful marker to predict prognosis and possibly, candidate for target therapy.
publishDate 2021
dc.date.issued.fl_str_mv 2021-07-01
dc.date.accessioned.fl_str_mv 2022-12-06T17:39:16Z
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dc.identifier.citation.fl_str_mv SOARES, Rossy-Eric Pereira. Expressão da tetraspanina (CD81) em mieloblastos e sua associação com o perfil de citocinas Th2 e prognóstico adverso em leucemia mielóide aguda. 2021.129 f. Tese (Programa de Pós-Graduação em Ciências da Saúde/CCBS) - Universidade Federal do Maranhão, São Luís, 2021
dc.identifier.uri.fl_str_mv https://tedebc.ufma.br/jspui/handle/tede/tede/4395
identifier_str_mv SOARES, Rossy-Eric Pereira. Expressão da tetraspanina (CD81) em mieloblastos e sua associação com o perfil de citocinas Th2 e prognóstico adverso em leucemia mielóide aguda. 2021.129 f. Tese (Programa de Pós-Graduação em Ciências da Saúde/CCBS) - Universidade Federal do Maranhão, São Luís, 2021
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dc.publisher.initials.fl_str_mv UFMA
dc.publisher.country.fl_str_mv Brasil
dc.publisher.department.fl_str_mv DEPARTAMENTO DE BIOLOGIA/CCBS
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