Evaluation of miR-15a, miR-16-1, ZAP-70, Ang-2, and Bcl-2 as potential prognostic biomarkers in chronic lymphocytic leukemia

Detalhes bibliográficos
Autor(a) principal: Vieira Braga, Tatiane
Data de Publicação: 2022
Outros Autores: Cristina Gontijo Evangelista, Fernanda, Santiago, Marie Gabriele, Menezes Ferrão, Aline Lúcia, Dauare de Almeida, Tamara, Lima da Fonseca Barbosa, Bárbara, Schusterschitz da Silva Araujo, Sergio, Nogueira Ribeiro, Glaciano, Carvalho, Maria das Graças, de Paula Sabino, Adriano
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Brazilian Journal of Pharmaceutical Sciences
Texto Completo: https://www.revistas.usp.br/bjps/article/view/205963
Resumo: Chronic lymphocytic leukemia (CLL) is a blood cancer characterized by the accumulation of clonal B-lymphocytes. This study evaluated the mRNA gene expression of miR-15a, miR-16- 1, ZAP-70, and Ang-2 by qPCR, as well as the plasma levels of Bcl-2 by Elisa immunoassay, in CLL patients and healthy controls. Significant differences were observed when comparing patients and controls regarding miR-15a (p < 0.001), miR-16-1 (p < 0.001) mRNA, Ang-2 gene expression, and Bcl-2 plasma levels (p < 0.001). When stratified by risk, differences were maintained with a significantly reduced expression in high-risk patients. A positive correlation was observed between miR-15a and platelets (R2 = 0.340; p = 0.009) as well as between Bcl-2 and leukocytes (R2 = 0.310; p = 0.019). Conversely, negative correlations were observed between ZAP-70 and platelets (R2 = - 0.334; p = 0.011), between miR-15a and lymphocytes (R2 = - 0.376; p = 0.004), as well as between miR-16-and lymphocytes (R2 = - 0.515; p = 0.00004). The data suggest that a reduction in miR-15a and miR-16-1 expressions, in addition to an overexpression of Bcl-2, are associated with the reduction in apoptosis and, consequently, to a longer survival of lymphocytes, thus contributing to lymphocyte accumulation and aggravation of the disease. By contrast, Ang-2 expression was significantly higher in A than in B + C Binet groups. This context leads to the speculation that this biomarker should be investigated in more robust studies within populations with a still relevantly indolent form of the disease in an attempt to identify those patients with a greater potential for an aggravation of the disease.
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spelling Evaluation of miR-15a, miR-16-1, ZAP-70, Ang-2, and Bcl-2 as potential prognostic biomarkers in chronic lymphocytic leukemiaCLLmiR-15a miR-16-1BiomarkersChronic lymphocytic leukemia (CLL) is a blood cancer characterized by the accumulation of clonal B-lymphocytes. This study evaluated the mRNA gene expression of miR-15a, miR-16- 1, ZAP-70, and Ang-2 by qPCR, as well as the plasma levels of Bcl-2 by Elisa immunoassay, in CLL patients and healthy controls. Significant differences were observed when comparing patients and controls regarding miR-15a (p < 0.001), miR-16-1 (p < 0.001) mRNA, Ang-2 gene expression, and Bcl-2 plasma levels (p < 0.001). When stratified by risk, differences were maintained with a significantly reduced expression in high-risk patients. A positive correlation was observed between miR-15a and platelets (R2 = 0.340; p = 0.009) as well as between Bcl-2 and leukocytes (R2 = 0.310; p = 0.019). Conversely, negative correlations were observed between ZAP-70 and platelets (R2 = - 0.334; p = 0.011), between miR-15a and lymphocytes (R2 = - 0.376; p = 0.004), as well as between miR-16-and lymphocytes (R2 = - 0.515; p = 0.00004). The data suggest that a reduction in miR-15a and miR-16-1 expressions, in addition to an overexpression of Bcl-2, are associated with the reduction in apoptosis and, consequently, to a longer survival of lymphocytes, thus contributing to lymphocyte accumulation and aggravation of the disease. By contrast, Ang-2 expression was significantly higher in A than in B + C Binet groups. This context leads to the speculation that this biomarker should be investigated in more robust studies within populations with a still relevantly indolent form of the disease in an attempt to identify those patients with a greater potential for an aggravation of the disease.Universidade de São Paulo. Faculdade de Ciências Farmacêuticas2022-12-19info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://www.revistas.usp.br/bjps/article/view/20596310.1590/s2175-97902022e19332Brazilian Journal of Pharmaceutical Sciences; Vol. 58 (2022)Brazilian Journal of Pharmaceutical Sciences; v. 58 (2022)Brazilian Journal of Pharmaceutical Sciences; Vol. 58 (2022)2175-97901984-8250reponame:Brazilian Journal of Pharmaceutical Sciencesinstname:Universidade de São Paulo (USP)instacron:USPenghttps://www.revistas.usp.br/bjps/article/view/205963/194524Copyright (c) 2022 Brazilian Journal of Pharmaceutical Scienceshttps://creativecommons.org/licenses/by/4.0info:eu-repo/semantics/openAccessVieira Braga, TatianeCristina Gontijo Evangelista, FernandaSantiago, Marie GabrieleMenezes Ferrão, Aline LúciaDauare de Almeida, TamaraLima da Fonseca Barbosa, Bárbara Schusterschitz da Silva Araujo, SergioNogueira Ribeiro, Glaciano Carvalho, Maria das Graçasde Paula Sabino, Adriano2023-05-29T13:24:41Zoai:revistas.usp.br:article/205963Revistahttps://www.revistas.usp.br/bjps/indexPUBhttps://old.scielo.br/oai/scielo-oai.phpbjps@usp.br||elizabeth.igne@gmail.com2175-97901984-8250opendoar:2023-05-29T13:24:41Brazilian Journal of Pharmaceutical Sciences - Universidade de São Paulo (USP)false
dc.title.none.fl_str_mv Evaluation of miR-15a, miR-16-1, ZAP-70, Ang-2, and Bcl-2 as potential prognostic biomarkers in chronic lymphocytic leukemia
title Evaluation of miR-15a, miR-16-1, ZAP-70, Ang-2, and Bcl-2 as potential prognostic biomarkers in chronic lymphocytic leukemia
spellingShingle Evaluation of miR-15a, miR-16-1, ZAP-70, Ang-2, and Bcl-2 as potential prognostic biomarkers in chronic lymphocytic leukemia
Vieira Braga, Tatiane
CLL
miR-15a
miR-16-1
Biomarkers
title_short Evaluation of miR-15a, miR-16-1, ZAP-70, Ang-2, and Bcl-2 as potential prognostic biomarkers in chronic lymphocytic leukemia
title_full Evaluation of miR-15a, miR-16-1, ZAP-70, Ang-2, and Bcl-2 as potential prognostic biomarkers in chronic lymphocytic leukemia
title_fullStr Evaluation of miR-15a, miR-16-1, ZAP-70, Ang-2, and Bcl-2 as potential prognostic biomarkers in chronic lymphocytic leukemia
title_full_unstemmed Evaluation of miR-15a, miR-16-1, ZAP-70, Ang-2, and Bcl-2 as potential prognostic biomarkers in chronic lymphocytic leukemia
title_sort Evaluation of miR-15a, miR-16-1, ZAP-70, Ang-2, and Bcl-2 as potential prognostic biomarkers in chronic lymphocytic leukemia
author Vieira Braga, Tatiane
author_facet Vieira Braga, Tatiane
Cristina Gontijo Evangelista, Fernanda
Santiago, Marie Gabriele
Menezes Ferrão, Aline Lúcia
Dauare de Almeida, Tamara
Lima da Fonseca Barbosa, Bárbara
Schusterschitz da Silva Araujo, Sergio
Nogueira Ribeiro, Glaciano
Carvalho, Maria das Graças
de Paula Sabino, Adriano
author_role author
author2 Cristina Gontijo Evangelista, Fernanda
Santiago, Marie Gabriele
Menezes Ferrão, Aline Lúcia
Dauare de Almeida, Tamara
Lima da Fonseca Barbosa, Bárbara
Schusterschitz da Silva Araujo, Sergio
Nogueira Ribeiro, Glaciano
Carvalho, Maria das Graças
de Paula Sabino, Adriano
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Vieira Braga, Tatiane
Cristina Gontijo Evangelista, Fernanda
Santiago, Marie Gabriele
Menezes Ferrão, Aline Lúcia
Dauare de Almeida, Tamara
Lima da Fonseca Barbosa, Bárbara
Schusterschitz da Silva Araujo, Sergio
Nogueira Ribeiro, Glaciano
Carvalho, Maria das Graças
de Paula Sabino, Adriano
dc.subject.por.fl_str_mv CLL
miR-15a
miR-16-1
Biomarkers
topic CLL
miR-15a
miR-16-1
Biomarkers
description Chronic lymphocytic leukemia (CLL) is a blood cancer characterized by the accumulation of clonal B-lymphocytes. This study evaluated the mRNA gene expression of miR-15a, miR-16- 1, ZAP-70, and Ang-2 by qPCR, as well as the plasma levels of Bcl-2 by Elisa immunoassay, in CLL patients and healthy controls. Significant differences were observed when comparing patients and controls regarding miR-15a (p < 0.001), miR-16-1 (p < 0.001) mRNA, Ang-2 gene expression, and Bcl-2 plasma levels (p < 0.001). When stratified by risk, differences were maintained with a significantly reduced expression in high-risk patients. A positive correlation was observed between miR-15a and platelets (R2 = 0.340; p = 0.009) as well as between Bcl-2 and leukocytes (R2 = 0.310; p = 0.019). Conversely, negative correlations were observed between ZAP-70 and platelets (R2 = - 0.334; p = 0.011), between miR-15a and lymphocytes (R2 = - 0.376; p = 0.004), as well as between miR-16-and lymphocytes (R2 = - 0.515; p = 0.00004). The data suggest that a reduction in miR-15a and miR-16-1 expressions, in addition to an overexpression of Bcl-2, are associated with the reduction in apoptosis and, consequently, to a longer survival of lymphocytes, thus contributing to lymphocyte accumulation and aggravation of the disease. By contrast, Ang-2 expression was significantly higher in A than in B + C Binet groups. This context leads to the speculation that this biomarker should be investigated in more robust studies within populations with a still relevantly indolent form of the disease in an attempt to identify those patients with a greater potential for an aggravation of the disease.
publishDate 2022
dc.date.none.fl_str_mv 2022-12-19
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv https://www.revistas.usp.br/bjps/article/view/205963
10.1590/s2175-97902022e19332
url https://www.revistas.usp.br/bjps/article/view/205963
identifier_str_mv 10.1590/s2175-97902022e19332
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv https://www.revistas.usp.br/bjps/article/view/205963/194524
dc.rights.driver.fl_str_mv Copyright (c) 2022 Brazilian Journal of Pharmaceutical Sciences
https://creativecommons.org/licenses/by/4.0
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Copyright (c) 2022 Brazilian Journal of Pharmaceutical Sciences
https://creativecommons.org/licenses/by/4.0
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Universidade de São Paulo. Faculdade de Ciências Farmacêuticas
publisher.none.fl_str_mv Universidade de São Paulo. Faculdade de Ciências Farmacêuticas
dc.source.none.fl_str_mv Brazilian Journal of Pharmaceutical Sciences; Vol. 58 (2022)
Brazilian Journal of Pharmaceutical Sciences; v. 58 (2022)
Brazilian Journal of Pharmaceutical Sciences; Vol. 58 (2022)
2175-9790
1984-8250
reponame:Brazilian Journal of Pharmaceutical Sciences
instname:Universidade de São Paulo (USP)
instacron:USP
instname_str Universidade de São Paulo (USP)
instacron_str USP
institution USP
reponame_str Brazilian Journal of Pharmaceutical Sciences
collection Brazilian Journal of Pharmaceutical Sciences
repository.name.fl_str_mv Brazilian Journal of Pharmaceutical Sciences - Universidade de São Paulo (USP)
repository.mail.fl_str_mv bjps@usp.br||elizabeth.igne@gmail.com
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