Toll-like Receptors 2, 3, and 4 in Childhood Acute Lymphocytic Leukemia

Detalhes bibliográficos
Autor(a) principal: Cruz, Matheus Loureiro da Silva
Data de Publicação: 2023
Outros Autores: Santos, Rafael Pereira dos, Souza, Barbara Kunzler, Jaeger, Mariane da Cunha, Silva, Camila Alves da, Gregianin, Lauro José, Loss, Jiseh Fagundes, Marques, Rebeca Ferreira, Brunetto, Algemir Lunardi, Brunetto, André Tesainer, Roesler, Rafael, Farias, Caroline Brunetto de
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Revista Brasileira de Cancerologia (Online)
Texto Completo: https://rbc.inca.gov.br/index.php/revista/article/view/3676
Resumo: Introduction: Acute lymphocytic leukemia (ALL) is the most common cancer type in children and accounts for 80% of pediatric leukemias. Novel targets are necessary to improve survival rates for refractory and relapsed disease. There is accumulating evidence that Toll-like Receptor (TLR) signaling may be associated with outcomes in cancer however little has been described in leukemias. Objective: Analyze the expression and contribution of TLRs to the development of childhood ALL. Method: To evaluate the effect of specific TLR2, TLR3, and TLR4 agonists on the viability and proliferation of childhood ALL cell lines and to analyzed the mRNA expression of these types of TLR in bone marrow blast cells at diagnosis (D0) and induction (D35) in pediatric ALL patients. Results: Treatment with TLR agonists reduced the cell viability of Jurkat and Sup-B15 cell lines. Cell cycle distribution in Jurkat was altered, reducing polyploid cells and increasing sub-G1 phase. Conclusion: It was observed that the cell viability of the cell lines responded with different sensitivities to the agonists. The polyploidy associated with tumor malignancy was reduced, in addition to the increase in the sub-G1 phase indicating an increase in apoptosis. There were differences in TLR expression at D35 between groups at risk of the disease. Patients with high expression of TLR2 and low expression of TLR4 on D35 demonstrated a worse prognosis.
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spelling Toll-like Receptors 2, 3, and 4 in Childhood Acute Lymphocytic LeukemiaReceptores Tipo Toll 2, 3 y 4 en la Leucemia Linfocítica Aguda InfantilReceptores do Tipo Toll 2, 3 e 4 em Leucemia Linfocítica Aguda Infantilleucemia-linfoma linfoblástico de células precursorasreceptores Toll-likeprecursor cell lymphoblastic leukemia-lymphomaToll-like receptorsleucemia-linfoma linfoblástico de células precursorasreceptores Toll-likeIntroduction: Acute lymphocytic leukemia (ALL) is the most common cancer type in children and accounts for 80% of pediatric leukemias. Novel targets are necessary to improve survival rates for refractory and relapsed disease. There is accumulating evidence that Toll-like Receptor (TLR) signaling may be associated with outcomes in cancer however little has been described in leukemias. Objective: Analyze the expression and contribution of TLRs to the development of childhood ALL. Method: To evaluate the effect of specific TLR2, TLR3, and TLR4 agonists on the viability and proliferation of childhood ALL cell lines and to analyzed the mRNA expression of these types of TLR in bone marrow blast cells at diagnosis (D0) and induction (D35) in pediatric ALL patients. Results: Treatment with TLR agonists reduced the cell viability of Jurkat and Sup-B15 cell lines. Cell cycle distribution in Jurkat was altered, reducing polyploid cells and increasing sub-G1 phase. Conclusion: It was observed that the cell viability of the cell lines responded with different sensitivities to the agonists. The polyploidy associated with tumor malignancy was reduced, in addition to the increase in the sub-G1 phase indicating an increase in apoptosis. There were differences in TLR expression at D35 between groups at risk of the disease. Patients with high expression of TLR2 and low expression of TLR4 on D35 demonstrated a worse prognosis.Introducción: La leucemia linfocítica aguda (LLA) es el tipo de cáncer más común en los ninos y representa el 80 % de las leucemias pediátricas. Se necesitan nuevos objetivos para mejorar las tasas de supervivencia de la enfermedad refractaria y recidivante. Cada vez hay más pruebas de que la senalización del receptor Toll-Like (TLR) puede estar asociada con resultados en el cáncer, aunque se ha descrito poco en las leucemias. Objetivo: Analizar la expresión y la contribución de los TLR al desarrollo de la LLA infantil. Método: Evaluar el efecto de agonistas específicos de TLR2, TLR3 y TLR4 en la viabilidad y proliferación de líneas celulares de LLA infantil y analizar la expresión de ARNm de estos tipos de TLR en células blásticas de médula ósea en el momento del diagnóstico (D0) y la inducción (D35) en pacientes pediátricos con LLA. Resultados: El tratamiento con agonistas de TLR redujo la viabilidad celular de las líneas celulares Jurkat y sup-B15. Se alteró la distribución del ciclo celular en Jurkat, reduciendo las células poliploides y aumentando la fase sub-G1. Hubo un aumento en la expresión de los receptores entre D0 y D35 en muestras de pacientes. Conclusión: Se observó que la viabilidad celular de las líneas celulares respondía con distintas sensibilidades a los agonistas. Se redujo la poliploidía asociada con la malignidad del tumor, además de un aumento de la fase sub-G1 que indica un aumento de la apoptosis. Hubo diferencias en la expresión de TLR en D35 entre los grupos de riesgo de enfermedad. Los pacientes con alta expresión de TLR2 y baja expresión de TLR4 en D35 mostraron peor pronóstico.Introdução: A leucemia linfoblástica aguda (LLA) é o tipo de câncer mais comum em crianças e representa 80% das leucemias pediátricas. Novos alvos são necessários para melhorar as taxas de sobrevivência para doença refratária e recidivante. Há evidências acumuladas de que a sinalização de receptores Toll-Like (TLR) pode estar associada a resultados em câncer, embora pouco tenha sido descrito em leucemias. Objetivo: Analisar a expressão e a contribuição dos TLR para o desenvolvimento da LLA infantil. Método: Avaliar o efeito de agonistas específicos de TLR2, TLR3 e TLR4 na viabilidade e proliferação de linhagens celulares de LLA infantil e analisar a expressão do RNAm desses tipos de TLR em células blásticas da medula óssea no diagnóstico (D0) e na indução (D35) em pacientes LLA pediátricos. Resultados: O tratamento com agonistas de TLR reduziu a viabilidade celular das linhagens celulares Jurkat e Sup-B15. A distribuição do ciclo celular em Jurkat foi alterada, reduzindo as células poliploides e aumentando a fase sub-G1. Houve aumento na expressão dos receptores entre D0 e D35 em amostras de pacientes. Conclusão: Observou-se que a viabilidade celular das linhagens celulares respondeu com diferentes sensibilidades aos agonistas. A poliploidia associada a malignidade tumoral foi reduzida, além de o aumento da fase sub-G1 indicar aumento da apoptose. Houve diferenças na expressão de TLR em D35 entre os grupos de risco da doença. Pacientes com alta expressão de TLR2 e baixa expressão de TLR4 no D35 demonstraram pior prognóstico.INCA2023-07-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionArtigos, Avaliado pelos paresapplication/pdftext/htmlhttps://rbc.inca.gov.br/index.php/revista/article/view/367610.32635/2176-9745.RBC.2023v69n3.3676Revista Brasileira de Cancerologia; Vol. 69 No. 3 (2023): July/Aug./Sept.; e-053676Revista Brasileira de Cancerologia; Vol. 69 Núm. 3 (2023): jul./ago./sept.; e-053676Revista Brasileira de Cancerologia; v. 69 n. 3 (2023): jul./ago./set.; e-0536762176-9745reponame:Revista Brasileira de Cancerologia (Online)instname:Instituto Nacional de Câncer José Alencar Gomes da Silva (INCA)instacron:INCAenghttps://rbc.inca.gov.br/index.php/revista/article/view/3676/3007https://rbc.inca.gov.br/index.php/revista/article/view/3676/3025Copyright (c) 2023 Revista Brasileira de Cancerologiahttps://creativecommons.org/licenses/by/4.0info:eu-repo/semantics/openAccessCruz, Matheus Loureiro da SilvaSantos, Rafael Pereira dosSouza, Barbara KunzlerJaeger, Mariane da CunhaSilva, Camila Alves daGregianin, Lauro JoséLoss, Jiseh FagundesMarques, Rebeca FerreiraBrunetto, Algemir LunardiBrunetto, André TesainerRoesler, RafaelFarias, Caroline Brunetto de2023-11-03T17:14:41Zoai:rbc.inca.gov.br:article/3676Revistahttps://rbc.inca.gov.br/index.php/revistaPUBhttps://rbc.inca.gov.br/index.php/revista/oairbc@inca.gov.br0034-71162176-9745opendoar:2023-11-03T17:14:41Revista Brasileira de Cancerologia (Online) - Instituto Nacional de Câncer José Alencar Gomes da Silva (INCA)false
dc.title.none.fl_str_mv Toll-like Receptors 2, 3, and 4 in Childhood Acute Lymphocytic Leukemia
Receptores Tipo Toll 2, 3 y 4 en la Leucemia Linfocítica Aguda Infantil
Receptores do Tipo Toll 2, 3 e 4 em Leucemia Linfocítica Aguda Infantil
title Toll-like Receptors 2, 3, and 4 in Childhood Acute Lymphocytic Leukemia
spellingShingle Toll-like Receptors 2, 3, and 4 in Childhood Acute Lymphocytic Leukemia
Cruz, Matheus Loureiro da Silva
leucemia-linfoma linfoblástico de células precursoras
receptores Toll-like
precursor cell lymphoblastic leukemia-lymphoma
Toll-like receptors
leucemia-linfoma linfoblástico de células precursoras
receptores Toll-like
title_short Toll-like Receptors 2, 3, and 4 in Childhood Acute Lymphocytic Leukemia
title_full Toll-like Receptors 2, 3, and 4 in Childhood Acute Lymphocytic Leukemia
title_fullStr Toll-like Receptors 2, 3, and 4 in Childhood Acute Lymphocytic Leukemia
title_full_unstemmed Toll-like Receptors 2, 3, and 4 in Childhood Acute Lymphocytic Leukemia
title_sort Toll-like Receptors 2, 3, and 4 in Childhood Acute Lymphocytic Leukemia
author Cruz, Matheus Loureiro da Silva
author_facet Cruz, Matheus Loureiro da Silva
Santos, Rafael Pereira dos
Souza, Barbara Kunzler
Jaeger, Mariane da Cunha
Silva, Camila Alves da
Gregianin, Lauro José
Loss, Jiseh Fagundes
Marques, Rebeca Ferreira
Brunetto, Algemir Lunardi
Brunetto, André Tesainer
Roesler, Rafael
Farias, Caroline Brunetto de
author_role author
author2 Santos, Rafael Pereira dos
Souza, Barbara Kunzler
Jaeger, Mariane da Cunha
Silva, Camila Alves da
Gregianin, Lauro José
Loss, Jiseh Fagundes
Marques, Rebeca Ferreira
Brunetto, Algemir Lunardi
Brunetto, André Tesainer
Roesler, Rafael
Farias, Caroline Brunetto de
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Cruz, Matheus Loureiro da Silva
Santos, Rafael Pereira dos
Souza, Barbara Kunzler
Jaeger, Mariane da Cunha
Silva, Camila Alves da
Gregianin, Lauro José
Loss, Jiseh Fagundes
Marques, Rebeca Ferreira
Brunetto, Algemir Lunardi
Brunetto, André Tesainer
Roesler, Rafael
Farias, Caroline Brunetto de
dc.subject.por.fl_str_mv leucemia-linfoma linfoblástico de células precursoras
receptores Toll-like
precursor cell lymphoblastic leukemia-lymphoma
Toll-like receptors
leucemia-linfoma linfoblástico de células precursoras
receptores Toll-like
topic leucemia-linfoma linfoblástico de células precursoras
receptores Toll-like
precursor cell lymphoblastic leukemia-lymphoma
Toll-like receptors
leucemia-linfoma linfoblástico de células precursoras
receptores Toll-like
description Introduction: Acute lymphocytic leukemia (ALL) is the most common cancer type in children and accounts for 80% of pediatric leukemias. Novel targets are necessary to improve survival rates for refractory and relapsed disease. There is accumulating evidence that Toll-like Receptor (TLR) signaling may be associated with outcomes in cancer however little has been described in leukemias. Objective: Analyze the expression and contribution of TLRs to the development of childhood ALL. Method: To evaluate the effect of specific TLR2, TLR3, and TLR4 agonists on the viability and proliferation of childhood ALL cell lines and to analyzed the mRNA expression of these types of TLR in bone marrow blast cells at diagnosis (D0) and induction (D35) in pediatric ALL patients. Results: Treatment with TLR agonists reduced the cell viability of Jurkat and Sup-B15 cell lines. Cell cycle distribution in Jurkat was altered, reducing polyploid cells and increasing sub-G1 phase. Conclusion: It was observed that the cell viability of the cell lines responded with different sensitivities to the agonists. The polyploidy associated with tumor malignancy was reduced, in addition to the increase in the sub-G1 phase indicating an increase in apoptosis. There were differences in TLR expression at D35 between groups at risk of the disease. Patients with high expression of TLR2 and low expression of TLR4 on D35 demonstrated a worse prognosis.
publishDate 2023
dc.date.none.fl_str_mv 2023-07-06
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
Artigos, Avaliado pelos pares
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv https://rbc.inca.gov.br/index.php/revista/article/view/3676
10.32635/2176-9745.RBC.2023v69n3.3676
url https://rbc.inca.gov.br/index.php/revista/article/view/3676
identifier_str_mv 10.32635/2176-9745.RBC.2023v69n3.3676
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv https://rbc.inca.gov.br/index.php/revista/article/view/3676/3007
https://rbc.inca.gov.br/index.php/revista/article/view/3676/3025
dc.rights.driver.fl_str_mv Copyright (c) 2023 Revista Brasileira de Cancerologia
https://creativecommons.org/licenses/by/4.0
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Copyright (c) 2023 Revista Brasileira de Cancerologia
https://creativecommons.org/licenses/by/4.0
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
text/html
dc.publisher.none.fl_str_mv INCA
publisher.none.fl_str_mv INCA
dc.source.none.fl_str_mv Revista Brasileira de Cancerologia; Vol. 69 No. 3 (2023): July/Aug./Sept.; e-053676
Revista Brasileira de Cancerologia; Vol. 69 Núm. 3 (2023): jul./ago./sept.; e-053676
Revista Brasileira de Cancerologia; v. 69 n. 3 (2023): jul./ago./set.; e-053676
2176-9745
reponame:Revista Brasileira de Cancerologia (Online)
instname:Instituto Nacional de Câncer José Alencar Gomes da Silva (INCA)
instacron:INCA
instname_str Instituto Nacional de Câncer José Alencar Gomes da Silva (INCA)
instacron_str INCA
institution INCA
reponame_str Revista Brasileira de Cancerologia (Online)
collection Revista Brasileira de Cancerologia (Online)
repository.name.fl_str_mv Revista Brasileira de Cancerologia (Online) - Instituto Nacional de Câncer José Alencar Gomes da Silva (INCA)
repository.mail.fl_str_mv rbc@inca.gov.br
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