Avaliação molecular de AURKA, AURKB e PLK1 no processo de leucemogênese em pacientes portadores de Leucemia Mieloide aguda no estado do Ceará

Detalhes bibliográficos
Ano de defesa: 2025
Autor(a) principal: Machado, Anna Karolyna da Costa
Orientador(a): Nunes, Caroline de Fátima Aquino Moreira
Banca de defesa: Não Informado pela instituição
Tipo de documento: Dissertação
Tipo de acesso: Acesso aberto
Idioma: por
Instituição de defesa: Não Informado pela instituição
Programa de Pós-Graduação: Não Informado pela instituição
Departamento: Não Informado pela instituição
País: Não Informado pela instituição
Área do conhecimento CNPq:
Link de acesso: http://repositorio.ufc.br/handle/riufc/82543
Resumo: Acute myeloid leukemia (AML) is one of the most aggressive types of leukemia, represented by the clonal proliferation of myeloid precursors, which mainly promotes quantitative and differentiation alterations, as well as suppression of normal hematopoiesis. Throughout leukemogenesis, modifications may occur in several elements that make up cellular signaling pathways, among which we highlight the AURKA, AURKB, and PLK1 proteins, which are directly related to cell cycle control and cell proliferation. This study investigated the hematological profile and the expression of the AURKA, AURKB, and PLK1 genes in a cohort of individuals with AML, in order to understand their roles in the pathophysiology of the disease. The analyses revealed a significant underexpression of AURKA in the bone marrow of patients compared to the control group (p = 0.0254) and an overexpression of PLK1 both in bone marrow (p < 0.0001) and in peripheral blood (p = 0.0144). In contrast, AURKB did not show a significant difference. Our data suggest that the low expression of AURKA is associated with the suppression of normal hematopoiesis due to the reduction of healthy blast cells and/or the quiescent state of the cells as a result of leukemic infiltration, which rely on alternative mechanisms to proliferate, possibly mediated by the activity of PLK1, which in our study showed increased expression. Furthermore, our results also point to PLK1 as a potential biomarker for the presence of the disease, since its overexpression did not differ with respect to gender, risk stratification, or age of the individuals. Finally, survival analyses indicate that AURKA expression in the bone marrow is associated with a protective factor and increased patient survival, and that those with higher expression of the three target genes had a lower mortality rate (p = 0.043).
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spelling Machado, Anna Karolyna da CostaNunes, Caroline de Fátima Aquino Moreira2025-09-16T13:30:56Z2025-09-16T13:30:56Z2025MACHADO, Anna Karolyna da Costa. Avaliação molecular de AURKA, AURKB e PLK1 no processo de leucemogênese em pacientes portadores de Leucemia Mieloide aguda no estado do Ceará. 2025. Dissertação (Mestrado em Medicina Translacional) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza 2025. Disponível em: http://www.repositorio.ufc.br/handle/riufc/ 82543. Acesso em: 16 set. 2025.http://repositorio.ufc.br/handle/riufc/82543Acute myeloid leukemia (AML) is one of the most aggressive types of leukemia, represented by the clonal proliferation of myeloid precursors, which mainly promotes quantitative and differentiation alterations, as well as suppression of normal hematopoiesis. Throughout leukemogenesis, modifications may occur in several elements that make up cellular signaling pathways, among which we highlight the AURKA, AURKB, and PLK1 proteins, which are directly related to cell cycle control and cell proliferation. This study investigated the hematological profile and the expression of the AURKA, AURKB, and PLK1 genes in a cohort of individuals with AML, in order to understand their roles in the pathophysiology of the disease. The analyses revealed a significant underexpression of AURKA in the bone marrow of patients compared to the control group (p = 0.0254) and an overexpression of PLK1 both in bone marrow (p < 0.0001) and in peripheral blood (p = 0.0144). In contrast, AURKB did not show a significant difference. Our data suggest that the low expression of AURKA is associated with the suppression of normal hematopoiesis due to the reduction of healthy blast cells and/or the quiescent state of the cells as a result of leukemic infiltration, which rely on alternative mechanisms to proliferate, possibly mediated by the activity of PLK1, which in our study showed increased expression. Furthermore, our results also point to PLK1 as a potential biomarker for the presence of the disease, since its overexpression did not differ with respect to gender, risk stratification, or age of the individuals. Finally, survival analyses indicate that AURKA expression in the bone marrow is associated with a protective factor and increased patient survival, and that those with higher expression of the three target genes had a lower mortality rate (p = 0.043).A leucemia mieloide aguda (LMA) é uma das leucemias mais agressiva representada pela proliferação clonal de precursores mieloides, que promovem alterações, principalmente, quantitativas e de diferenciação celular e pela supressão da hematopoese normal. Ao longo da leucemogênese, podem ocorrer modificações em diversos elementos que compõem vias de sinalizações celulares, dentre eles podemos ressaltar as proteínas AURKA, AURKB e PLK1, que possuem relação direta com o controle do ciclo e a proliferação celular. Este estudo investigou o perfil hematológico e a expressão dos genes AURKA, AURKB e PLK1 em uma coorte com portadores de LMA, a fim de compreender seus papéis na fisiopatologia da doença. As análises revelaram uma hipoexpressão significativa de AURKA na medula óssea dos pacientes em comparação ao grupo controle (p=0,0254) e uma hiperexpressão de PLK1 tanto na medula óssea (p<0,0001), quanto no sangue periférico (p=0,0144). Em contrapartida, AURKB não mostrou diferença significativa. Nossos dados sugerem que a baixa expressão de AURKA associa-se a supressão da hematopoese normal pela redução das células blásticas saudáveis e/ou pelo estado quiescente das células em decorrência da infiltração leucêmica, que recorrem a mecanismos alternativos para se proliferarem, possivelmente mediados pela atividade de PLK1 que em nosso estudo mostrou-se com aumento de expressão. Além disso, nossos resultados também apontam PLK1 como um potencial biomarcador de presença da doença, uma vez que sua hiperexpressão não diferiu com relação aos gêneros e nem quanto às estratificações de risco e as idades dos indivíduos. Por fim, as análises de sobrevida apontam que a AURKA na medula óssea está associada a um fator protetor e prolongamento da vida dos pacientes e que aqueles com maiores expressões dos três genes-alvos tiveram um menor índice de morte (p=0,043).Avaliação molecular de AURKA, AURKB e PLK1 no processo de leucemogênese em pacientes portadores de Leucemia Mieloide aguda no estado do Cearáinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisLeucemia Mieloide AgudaExpressão GênicaBiomarcadoresAurora QuinasesQuinase 1 Polo-likeLeukemia, Myeloid, AcuteGene ExpressionBiomarkersAurora kinasesPolo-Like Kinase 1CNPQ::CIENCIAS DA SAUDE::MEDICINAinfo:eu-repo/semantics/openAccessporreponame:Repositório Institucional da Universidade Federal do Ceará (UFC)instname:Universidade Federal do Ceará (UFC)instacron:UFChttps://orcid.org/0000-0003-0802-6320http://lattes.cnpq.br/5522801608795556https://orcid.org/0000-0001-5845-3481http://lattes.cnpq.br/3191425896154552LICENSElicense.txtlicense.txttext/plain; charset=utf-81748http://repositorio.ufc.br/bitstream/riufc/82543/4/license.txt8a4605be74aa9ea9d79846c1fba20a33MD54ORIGINAL2025_dis_akcmachado.pdf2025_dis_akcmachado.pdfapplication/pdf1952925http://repositorio.ufc.br/bitstream/riufc/82543/1/2025_dis_akcmachado.pdf014d5866b5015010c886ae44f7c8d2daMD51riufc/825432025-09-16 10:32:35.735oai:repositorio.ufc.br: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Repositório InstitucionalPUBhttp://www.repositorio.ufc.br/ri-oai/requestbu@ufc.br || repositorio@ufc.bropendoar:2025-09-16T13:32:35Repositório Institucional da Universidade Federal do Ceará (UFC) - Universidade Federal do Ceará (UFC)false
dc.title.pt_BR.fl_str_mv Avaliação molecular de AURKA, AURKB e PLK1 no processo de leucemogênese em pacientes portadores de Leucemia Mieloide aguda no estado do Ceará
title Avaliação molecular de AURKA, AURKB e PLK1 no processo de leucemogênese em pacientes portadores de Leucemia Mieloide aguda no estado do Ceará
spellingShingle Avaliação molecular de AURKA, AURKB e PLK1 no processo de leucemogênese em pacientes portadores de Leucemia Mieloide aguda no estado do Ceará
Machado, Anna Karolyna da Costa
CNPQ::CIENCIAS DA SAUDE::MEDICINA
Leucemia Mieloide Aguda
Expressão Gênica
Biomarcadores
Aurora Quinases
Quinase 1 Polo-like
Leukemia, Myeloid, Acute
Gene Expression
Biomarkers
Aurora kinases
Polo-Like Kinase 1
title_short Avaliação molecular de AURKA, AURKB e PLK1 no processo de leucemogênese em pacientes portadores de Leucemia Mieloide aguda no estado do Ceará
title_full Avaliação molecular de AURKA, AURKB e PLK1 no processo de leucemogênese em pacientes portadores de Leucemia Mieloide aguda no estado do Ceará
title_fullStr Avaliação molecular de AURKA, AURKB e PLK1 no processo de leucemogênese em pacientes portadores de Leucemia Mieloide aguda no estado do Ceará
title_full_unstemmed Avaliação molecular de AURKA, AURKB e PLK1 no processo de leucemogênese em pacientes portadores de Leucemia Mieloide aguda no estado do Ceará
title_sort Avaliação molecular de AURKA, AURKB e PLK1 no processo de leucemogênese em pacientes portadores de Leucemia Mieloide aguda no estado do Ceará
author Machado, Anna Karolyna da Costa
author_facet Machado, Anna Karolyna da Costa
author_role author
dc.contributor.author.fl_str_mv Machado, Anna Karolyna da Costa
dc.contributor.advisor1.fl_str_mv Nunes, Caroline de Fátima Aquino Moreira
contributor_str_mv Nunes, Caroline de Fátima Aquino Moreira
dc.subject.cnpq.fl_str_mv CNPQ::CIENCIAS DA SAUDE::MEDICINA
topic CNPQ::CIENCIAS DA SAUDE::MEDICINA
Leucemia Mieloide Aguda
Expressão Gênica
Biomarcadores
Aurora Quinases
Quinase 1 Polo-like
Leukemia, Myeloid, Acute
Gene Expression
Biomarkers
Aurora kinases
Polo-Like Kinase 1
dc.subject.ptbr.pt_BR.fl_str_mv Leucemia Mieloide Aguda
Expressão Gênica
Biomarcadores
Aurora Quinases
Quinase 1 Polo-like
dc.subject.en.pt_BR.fl_str_mv Leukemia, Myeloid, Acute
Gene Expression
Biomarkers
Aurora kinases
Polo-Like Kinase 1
description Acute myeloid leukemia (AML) is one of the most aggressive types of leukemia, represented by the clonal proliferation of myeloid precursors, which mainly promotes quantitative and differentiation alterations, as well as suppression of normal hematopoiesis. Throughout leukemogenesis, modifications may occur in several elements that make up cellular signaling pathways, among which we highlight the AURKA, AURKB, and PLK1 proteins, which are directly related to cell cycle control and cell proliferation. This study investigated the hematological profile and the expression of the AURKA, AURKB, and PLK1 genes in a cohort of individuals with AML, in order to understand their roles in the pathophysiology of the disease. The analyses revealed a significant underexpression of AURKA in the bone marrow of patients compared to the control group (p = 0.0254) and an overexpression of PLK1 both in bone marrow (p < 0.0001) and in peripheral blood (p = 0.0144). In contrast, AURKB did not show a significant difference. Our data suggest that the low expression of AURKA is associated with the suppression of normal hematopoiesis due to the reduction of healthy blast cells and/or the quiescent state of the cells as a result of leukemic infiltration, which rely on alternative mechanisms to proliferate, possibly mediated by the activity of PLK1, which in our study showed increased expression. Furthermore, our results also point to PLK1 as a potential biomarker for the presence of the disease, since its overexpression did not differ with respect to gender, risk stratification, or age of the individuals. Finally, survival analyses indicate that AURKA expression in the bone marrow is associated with a protective factor and increased patient survival, and that those with higher expression of the three target genes had a lower mortality rate (p = 0.043).
publishDate 2025
dc.date.accessioned.fl_str_mv 2025-09-16T13:30:56Z
dc.date.available.fl_str_mv 2025-09-16T13:30:56Z
dc.date.issued.fl_str_mv 2025
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
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dc.identifier.citation.fl_str_mv MACHADO, Anna Karolyna da Costa. Avaliação molecular de AURKA, AURKB e PLK1 no processo de leucemogênese em pacientes portadores de Leucemia Mieloide aguda no estado do Ceará. 2025. Dissertação (Mestrado em Medicina Translacional) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza 2025. Disponível em: http://www.repositorio.ufc.br/handle/riufc/ 82543. Acesso em: 16 set. 2025.
dc.identifier.uri.fl_str_mv http://repositorio.ufc.br/handle/riufc/82543
identifier_str_mv MACHADO, Anna Karolyna da Costa. Avaliação molecular de AURKA, AURKB e PLK1 no processo de leucemogênese em pacientes portadores de Leucemia Mieloide aguda no estado do Ceará. 2025. Dissertação (Mestrado em Medicina Translacional) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza 2025. Disponível em: http://www.repositorio.ufc.br/handle/riufc/ 82543. Acesso em: 16 set. 2025.
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