Expressão da tetraspanina (CD81) em mieloblastos e sua associação com o perfil de citocinas Th2 e prognóstico adverso em leucemia mielóide aguda
Autor(a) principal: | |
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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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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). No. of bitstreams: 1 Rossy-Eric.pdf: 311783 bytes, checksum: 877cdb39fc1f67e1f47d2438da1cea31 (MD5) Previous issue date: 2021-07-01application/pdfporUniversidade Federal do MaranhãoPROGRAMA DE PÓS-GRADUAÇÃO EM CIÊNCIAS DA SAÚDE/CCBSUFMABrasilDEPARTAMENTO DE BIOLOGIA/CCBSCD81;LMA;citocinas;CD81;AML.CD81,AML,cytokines,prognosis.Ciências da SaúdeExpressão da tetraspanina (CD81) em mieloblastos e sua associação com o perfil de citocinas Th2 e prognóstico adverso em leucemia mielóide agudaTetraspanin (CD81) expression in myeloblasts and its association with the Th2 cytokine profile and adverse prognosis in acute myelogenous leukemiainfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da UFMAinstname:Universidade Federal do Maranhão (UFMA)instacron:UFMAORIGINALRossy-Eric.pdfRossy-Eric.pdfapplication/pdf311783http://tedebc.ufma.br:8080/bitstream/tede/4395/2/Rossy-Eric.pdf877cdb39fc1f67e1f47d2438da1cea31MD52LICENSElicense.txtlicense.txttext/plain; charset=utf-82255http://tedebc.ufma.br:8080/bitstream/tede/4395/1/license.txt97eeade1fce43278e63fe063657f8083MD51tede/43952022-12-06 14:39:16.117oai:tede2: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Biblioteca Digital de Teses e Dissertaçõeshttps://tedebc.ufma.br/jspui/PUBhttp://tedebc.ufma.br:8080/oai/requestrepositorio@ufma.br||repositorio@ufma.bropendoar:21312022-12-06T17:39:16Biblioteca Digital de Teses e Dissertações da UFMA - Universidade Federal do Maranhão (UFMA)false |
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 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/doctoralThesis |
format |
doctoralThesis |
status_str |
publishedVersion |
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 |
url |
https://tedebc.ufma.br/jspui/handle/tede/tede/4395 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
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openAccess |
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dc.publisher.none.fl_str_mv |
Universidade Federal do Maranhão |
dc.publisher.program.fl_str_mv |
PROGRAMA DE PÓS-GRADUAÇÃO EM CIÊNCIAS DA SAÚDE/CCBS |
dc.publisher.initials.fl_str_mv |
UFMA |
dc.publisher.country.fl_str_mv |
Brasil |
dc.publisher.department.fl_str_mv |
DEPARTAMENTO DE BIOLOGIA/CCBS |
publisher.none.fl_str_mv |
Universidade Federal do Maranhão |
dc.source.none.fl_str_mv |
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