PERFIL METABOLÔMICO IDENTIFICA ASSOCIAÇÃO DA VIA GLICOLÍTICA COM A RESISTÊNCIA À APARAGINASE EM LINHAGENS CELULARES DE LEUCEMIA LINFOBLÁSTICA AGUDA

Autores

DOI:

https://doi.org/10.61229/mpj.v1i1.2

Palavras-chave:

Metabolômica, Leucemia Linfoblástica Aguda, Resistência à Asparaginase

Resumo

A resposta precoce à terapia na leucemia linfoblástica aguda (LLA) pediátrica pode ser atribuída principalmente à resistência intrínseca dos linfoblastos leucêmicos à quimioterapia. Neste estudo, nosso objetivo foi determinar o perfil metabólico de linhagens celulares resistentes e sensíveis a L-asparaginase (ASNase) após o tratamento com a mesma utilizando metabolômica por RMN. As linhagens celulares de LLA Nalm6, Nalm21, REH e RS4;11 foram cultivadas em meio RPMI 1640 com 10% de SFB, suplementado ou não com ASNase (0,8 UI/ml). Após 24hs, os espectros de RMN do meio de cultura foram adquiridos e quantificados. A análise de PCA não supervisionada das concentrações obtidas dos metabólitos mostrou que o meio de cultura de células resistentes é caracterizado por níveis mais baixos de glicose e mais elevados de lactato. Curiosamente, a inibição da via da glicólise aumentou sinergicamente a sensibilidade das linhagens celulares resistentes à ASNase (Fsyn = 0,19 para Nalm6 e Fsyn = 0,50 para REH), mas não das sensíveis (Fsyn = 1,11 para Nalm21 e Fsyn = 1,85 para RS4;11). Concluindo, este estudo apresenta uma potencial abordagem metabolômica para a identificação não apenas de pacientes com possível resistência ao tratamento, mas também de moléculas-alvo para o desenvolvimento de futuras intervenções terapêuticas.

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Biografia do Autor

Carolina Pereira de Souza Melo, Boldrini Children’s Hospital, Campinas, SP, Brazil

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Publicado

23/02/2023

Como Citar

Melo, C. P. de S., Canevarolo, R. R., Brandalise, S. R., Zeri, A. C. de M., & Yunes, J. A. (2023). PERFIL METABOLÔMICO IDENTIFICA ASSOCIAÇÃO DA VIA GLICOLÍTICA COM A RESISTÊNCIA À APARAGINASE EM LINHAGENS CELULARES DE LEUCEMIA LINFOBLÁSTICA AGUDA. Mário Penna Journal, 1(1), 7–17. https://doi.org/10.61229/mpj.v1i1.2