Cathepsin B Is Not an Intrinsic Factor Related to Asparaginase Resistance of the Acute Lymphoblastic Leukemia REH Cell Line

Primer Autor
Monteiro, Gisele
Co-autores
Costa, Iris Munhoz
Effer, Brian
Costa-Silva, Tales Alexandre
Chen, Chen
Ciccone, Michael F.
Pessoa, Adalberto
dos Santos, Camila O.
Título
Cathepsin B Is Not an Intrinsic Factor Related to Asparaginase Resistance of the Acute Lymphoblastic Leukemia REH Cell Line
Editorial
MDPI
Revista
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Lenguaje
en
Resumen
L-Asparaginase (ASNase) is a biopharmaceutical used as an essential drug in the treatment of acute lymphoblastic leukemia (ALL). Yet, some cases of ALL are naturally resistant to ASNase treatment, which results in poor prognosis. The REH ALL cell line, used as a model for studying the most common subtype of ALL, is considered resistant to treatment with ASNase. Cathepsin B (CTSB) is one of the proteases involved in the regulation of in vivo ASNase serum half-life and it has also been associated with the progression and resistance to treatment of several solid tumors. Previous works have shown that, in vitro, ASNase is degraded when incubated with REH cell lysate, which is prevented by a specific CTSB inhibitor, suggesting a function of this protease in the ASNase resistance of REH cells. In this work, we utilized a combination of CRISPR/Cas9 gene targeting and enzymatic measurements to investigate the relevance of CTSB on ASNase treatment resistance in the ALL model cell line. We found that deletion of CTSB in REH ALL cells did not confer ASNase treatment sensitivity, thus suggesting that intrinsic expression of CTSB is not a mechanism that drives the resistant nature of these ALL cells to enzymes used as the first-line treatment against leukemia.
Fecha Publicación
2023
Tipo de Recurso
artículo original
doi
10.3390/ijms241311215
Formato Recurso
PDF
Palabras Claves
asparaginase
cathepsin B
acute lymphoblastic leukemia
treatment resistance
genetic editing
Ubicación del archivo
Categoría OCDE
Bioquímica y biología molecular
Química
Materias
asparaginasa
catepsina B
leucemia linfoblástica aguda
resistencia al tratamiento
edición genética
Identificador del recurso (Mandatado-único)
artículo original
Versión del recurso (Recomendado-único)
versión publicada
License
CC BY 4.0
Condición de la licencia (Recomendado-repetible)
CC BY 4.0
Derechos de acceso
acceso abierto
Access Rights
acceso abierto
Id de Web of Science
WOS:001030130400001
ISSN
1661-6596
Tipo de ruta
verde# dorado
Categoría WOS
Bioquímica y biología molecular
Química
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