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

Costa, Iris Munhoz, Effer, Brian, Costa-Silva, Tales Alexandre, Chen, Chen, Ciccone, Michael F, Pessoa, Adalberto, Dos Santos, Camila O, Monteiro, Gisele (July 2023) Cathepsin B Is Not an Intrinsic Factor Related to Asparaginase Resistance of the Acute Lymphoblastic Leukemia REH Cell Line. International Journal of Molecular Sciences, 24 (13). p. 11215. ISSN 1661-6596

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Abstract

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.

Item Type:	Paper
Subjects:	diseases & disorders > cancer diseases & disorders Investigative techniques and equipment organs, tissues, organelles, cell types and functions > cell types and functions > cell types > cell line organs, tissues, organelles, cell types and functions > cell types and functions > cell types > cell line organs, tissues, organelles, cell types and functions > cell types and functions > cell types > cell line Investigative techniques and equipment > CRISPR-Cas9 diseases & disorders > cancer > cancer types > leukemia diseases & disorders > cancer > cancer types
CSHL Authors:	Chen, Chen Ciccone, Michael F Dos Santos, Camila O. Munhoz Costa, Iris
Communities:	CSHL labs > Dos Santos lab
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	7 July 2023
Date Deposited:	21 Sep 2023 18:48
Last Modified:	08 Jan 2024 18:38
PMCID:	PMC10342508
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/40953

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