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dc.contributor.authorPereira, Daniele de Sá-
dc.date.available2023-11-13-
dc.date.available2023-11-21T13:12:38Z-
dc.date.issued2023-07-20-
dc.identifier.urihttp://repositorioinstitucional.uea.edu.br//handle/riuea/5352-
dc.description.abstractDespite therapeutic advances, 25% of children with acute lymphoblastic leukemia (ALL) relapse during treatment due to various intrinsic cellular switches. Studies report that the high expression of anti-apoptotic genes and resistance to multiple drugs are types associated with therapeutic failures in several neoplasms, including leukemias. However, there is a lack of studies demonstrating the influence of the expression of these genes on the response to induction therapy in patients with B-cell acute lymphoblastic leukemia (B-ALL). Thus, the present study aimed to characterize the expression of multi-drug resistance genes (ABCB1, ABCC1, MVP) and antiapoptotic genes (TP53 and BCL2) in the clinical prognosis of patients with B-ALL projected at Fundação Hospitalar de Hematologia e Hemoterapia do Amazonas (HEMOAM) and compare their expression levels to those of healthy children. A prospective longitudinal study was carried out, in which bone marrow (BM) and peripheral blood (SP) were included in 17 pediatric patients with BALL, of general age group and gender, during induction therapy, being collected at diagnosis (D0) and at the end of therapy (D35). In addition, a SP sample was collected from 17 healthy children, attended at the HEMOAM Foundation outpatient clinic. Detection of gene expression (ABCB1, ABCC1, MVP, TP53, BCL2) was performed using the quantitative real-time PCR (qPCR) technique using Taqman expression probes. It was observed that the anti-apoptotic genes BCL2 and TP53 were more expressed in patients with B-ALL compared to healthy subjects in SP. Furthermore, levels of expression of resistance genes ABCB1, ABCC1 and MVP decreased in the bone marrow at D35 of the induction therapy, counteracting the increase in expression of ABCC1 and MVP at D35 compared to D0 of reference blood from those patients. Finally, we observed that healthy individuals expressed higher levels of MVP compared to patients with ALL. Finally, we observed that the evaluation of the expression of the ABCB1, ABCC1, MVP, BCL2 and TP53 genes can help in the evaluation of the prognosis of these patients, contributing to the detection of possible molecular biomarkers and the creation of targeted therapies in addition to current chemotherapy. However, future investigations are necessary for a better understanding of the impact of the expression of these genes on medullary remission in these patients, generating data that contribute to an increase in the survival rate in A-ALL.pt_BR
dc.languageporpt_BR
dc.publisherUniversidade do Estado do Amazonaspt_BR
dc.rightsAcesso Abertopt_BR
dc.subjectLeucemia linfoblástica agudapt_BR
dc.subjectABCB1pt_BR
dc.subjectABCC1pt_BR
dc.subjectMVPpt_BR
dc.subjectTP53pt_BR
dc.subjectBCL2pt_BR
dc.subjectAcute lymphoblastic leukemiapt_BR
dc.titleCaracterização da expressão de genes antiapoptóticos e de resistência a múltiplas drogas na resposta a terapia de indução em pacientes com leucemia linfoblástica agudapt_BR
dc.title.alternativeCharacterization of the expression of antiapoptotic and multidrug resistance genes in response to induction therapy in patients with acute lymphoblastic leukemiapt_BR
dc.typeDissertaçãopt_BR
dc.date.accessioned2023-11-21T13:12:38Z-
dc.contributor.advisor-co1Marie, Adriana Malheiro Alle-
dc.contributor.advisor-co1Latteshttp://lattes.cnpq.br/2627415957053194pt_BR
dc.contributor.advisor1Costa, Allyson Guimarães da-
dc.contributor.advisor1Latteshttp://lattes.cnpq.br/7531662673281014pt_BR
dc.contributor.referee1Costa, Allyson Guimarães d-
dc.contributor.referee1Latteshttp://lattes.cnpq.br/7531662673281014pt_BR
dc.contributor.referee2Lima, Dhêmerson Souza de-
dc.contributor.referee2Latteshttp://lattes.cnpq.br/3461804562751268pt_BR
dc.contributor.referee3Mourão, Lucivana Prata de Souza-
dc.contributor.referee3Latteshttp://lattes.cnpq.br/1135734404648095pt_BR
dc.creator.Latteshttp://lattes.cnpq.br/8045746566975978pt_BR
dc.description.resumoApesar dos avanços terapêuticos, 25% das crianças com leucemia linfoblástica aguda (LLA) recaem durante o tratamento devido a diversos mecanismos celulares intrínsecos. Estudos relatam que a alta expressão de genes antiapoptóticos e de resistência a múltiplas drogas estão associados com falhas terapêuticas em vários tipos de neoplasias, incluindo as leucemias. Todavia, há uma carência de estudos que demonstrem a influência da expressão desses genes na resposta a terapia de indução em pacientes com leucemia linfoblástica aguda de células B (LLA-B). Assim, o presente estudo teve como objetivo caracterizar a expressão de genes de resistência a múltiplas drogas (ABCB1, ABCC1, MVP) e genes antiapoptóticos (TP53 e BCL2) no prognóstico clínico de pacientes com LLA-B diagnosticados na Fundação Hospitalar de Hematologia e Hemoterapia do Amazonas (HEMOAM) e comparar seus níveis de expressão aos de crianças saudáveis. Foi realizado um estudo longitudinal do tipo prospectivo, no qual foram incluídos amostras de medula óssea (MO) e sangue periférico (SP) de 17 pacientes pediátricos com LLA-B, de faixa etária geral e ambos os sexos, durante a terapia de indução, sendo coletadas ao diagnóstico (D0) e no final da terapia (D35). Adicionalmente, foi coletado amostras de SP de 17 crianças saudáveis, atendidas no ambulatorial da Fundação HEMOAM. A detecção da expressão dos genes (ABCB1, ABCC1, MVP, TP53, BCL2) ocorreu através da técnica de PCR quantitativa em tempo real (qPCR) utilizando sondas de expressão Taqman. Foi observado que os genes antiapoptóticos BCL2 e TP53 demonstraram serem mais expressos em pacientes com LLA-B em comparação a indivíduos saudáveis no SP. Além disso, níveis de expressão dos genes de resistência ABCB1, ABCC1 e MVP diminuíram na medula óssea ao D35 da terapia de indução, contrapondo o aumento na expressão de ABCC1 e MVP no D35 em comparação com D0 de amostras de sangue periférico desses pacientes. Por fim, observamos que indivíduos saudáveis expressaram níveis mais elevado de MVP em comparação a pacientes com LLA. Ao final do estudo, observamos que a avalição da expressão dos genes ABCB1,ABCC1, MVP, BCL2 e TP53 podem auxiliar na avaliação do prognóstico desses pacientes, contribuindo na detecção de possíveis biomarcadores moleculares e na criação de terapias alvos de forma agregada a quimioterapia atual. No entanto, investigações futuras são necessárias para o melhor entendimento do impacto da expressão desse genes na remissão medular nesses pacientes, gerando dados que contribuam com aumento da taxa de sobrevida na LLA-B.pt_BR
dc.publisher.countryBrasilpt_BR
dc.publisher.programPPGH -PROGRAMA DE PÓS-GRADUAÇÃO EM CIÊNCIAS APLICADAS À HEMATOLOGIApt_BR
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