Expresión de miRNAs en líneas celulares de Leucemia Mieloide Crónica expuestas a inhibidores de tirosina quinasa

Chronic myeloid leukemia is a clonal disease of the bone marrow characterized by a genetic marker: the t (9; 22) translocation. This genetic event produces an oncoprotein (BCR-ABL1) with constitutive tyrosine kinase activity which, through the phosphorylation of adapter proteins, will produce an inc...

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Autor principal: Freue, Julian Matias
Otros Autores: Bianchini, Michele
Formato: Tesis de maestría acceptedVersion
Lenguaje:Español
Publicado: Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica 2021
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Acceso en línea:http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=afamaster&cl=CL1&d=HWA_6877
https://repositoriouba.sisbi.uba.ar/gsdl/collect/afamaster/index/assoc/HWA_6877.dir/6877.PDF
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Sumario:Chronic myeloid leukemia is a clonal disease of the bone marrow characterized by a genetic marker: the t (9; 22) translocation. This genetic event produces an oncoprotein (BCR-ABL1) with constitutive tyrosine kinase activity which, through the phosphorylation of adapter proteins, will produce an increase in proliferation and decrease in apoptosis of hematopoietic precursors. Given the extensive myeloid proliferation that patients present, hyperleukocytosis is usually generated, which leads to diagnosis of the disease.\nAlthough this initial genetic translocation was believed to be the only responsible for the pathology, nowadays, other additional molecular events are being investigated.\nThe hypothesis of the work is that one of these events could be an alteration in the expression of microRNAs since t (9; 22) generates genomic instability and consequently additional genetic alterations to BCR-ABL1. This alteration would be independent of the BCR-ABL1 leading to cure a low percentage of patients.\nThrough qPCR analysis of a group of microRNAs in two cell lines exposed to imatinib and nilotinib, this dependence was evaluated.\nIn K562 cell line, a down regulation was observed when exposed to both drugs, with a dose-dependent effect.\nIn the MEG01 cell line a conclusive pattern was not observed in the change of expression.\nThe work did not allow to confirm the independence of microRNAs expression from the tyrosine kinase activity of BCR-ABL1.