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In Vitro Sensitivity to Venetoclax and Microenvironment Protection in Hairy Cell Leukemia

Current standard treatment of patients with hairy cell leukemia (HCL), a chronic B-cell neoplasia of low incidence that affects the elderly, is based on the administration of purine analogs such as cladribine. This chemotherapy approach shows satisfactory responses, but the disease relapses, often r...

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Autores principales: Vereertbrugghen, Alexia, Colado, Ana, Gargiulo, Ernesto, Bezares, Raimundo Fernando, Fernández Grecco, Horacio, Cordini, Gregorio, Custidiano, Maria del Rosario, François, Jean-Hugues, Berchem, Guy, Borge, Mercedes, Paggetti, Jerome, Moussay, Etienne, Gamberale, Romina, Giordano, Mirta, Morande, Pablo Elías
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8350736/
https://www.ncbi.nlm.nih.gov/pubmed/34381700
http://dx.doi.org/10.3389/fonc.2021.598319
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author Vereertbrugghen, Alexia
Colado, Ana
Gargiulo, Ernesto
Bezares, Raimundo Fernando
Fernández Grecco, Horacio
Cordini, Gregorio
Custidiano, Maria del Rosario
François, Jean-Hugues
Berchem, Guy
Borge, Mercedes
Paggetti, Jerome
Moussay, Etienne
Gamberale, Romina
Giordano, Mirta
Morande, Pablo Elías
author_facet Vereertbrugghen, Alexia
Colado, Ana
Gargiulo, Ernesto
Bezares, Raimundo Fernando
Fernández Grecco, Horacio
Cordini, Gregorio
Custidiano, Maria del Rosario
François, Jean-Hugues
Berchem, Guy
Borge, Mercedes
Paggetti, Jerome
Moussay, Etienne
Gamberale, Romina
Giordano, Mirta
Morande, Pablo Elías
author_sort Vereertbrugghen, Alexia
collection PubMed
description Current standard treatment of patients with hairy cell leukemia (HCL), a chronic B-cell neoplasia of low incidence that affects the elderly, is based on the administration of purine analogs such as cladribine. This chemotherapy approach shows satisfactory responses, but the disease relapses, often repeatedly. Venetoclax (ABT-199) is a Bcl-2 inhibitor currently approved for the treatment of chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML) in adult patients ineligible for intensive chemotherapy. Given that HCL cells express Bcl-2, our aim was to evaluate venetoclax as a potential therapy for HCL. We found that clinically relevant concentrations of venetoclax (0.1 and 1 µM) induced primary HCL cell apoptosis in vitro as measured by flow cytometry using Annexin V staining. As microenvironment induces resistance to venetoclax in CLL, we also evaluated its effect in HCL by testing the following stimuli: activated T lymphocytes, stromal cells, TLR-9 agonist CpG, and TLR-2 agonist PAM3. We found decreased levels of venetoclax-induced cytotoxicity in HCL cells exposed for 48 h to any of these stimuli, suggesting that leukemic B cells from HCL patients are sensitive to venetoclax, but this sensitivity can be overcome by signals from the microenvironment. We propose that the combination of venetoclax with drugs that target the microenvironment might improve its efficacy in HCL.
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spelling pubmed-83507362021-08-10 In Vitro Sensitivity to Venetoclax and Microenvironment Protection in Hairy Cell Leukemia Vereertbrugghen, Alexia Colado, Ana Gargiulo, Ernesto Bezares, Raimundo Fernando Fernández Grecco, Horacio Cordini, Gregorio Custidiano, Maria del Rosario François, Jean-Hugues Berchem, Guy Borge, Mercedes Paggetti, Jerome Moussay, Etienne Gamberale, Romina Giordano, Mirta Morande, Pablo Elías Front Oncol Oncology Current standard treatment of patients with hairy cell leukemia (HCL), a chronic B-cell neoplasia of low incidence that affects the elderly, is based on the administration of purine analogs such as cladribine. This chemotherapy approach shows satisfactory responses, but the disease relapses, often repeatedly. Venetoclax (ABT-199) is a Bcl-2 inhibitor currently approved for the treatment of chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML) in adult patients ineligible for intensive chemotherapy. Given that HCL cells express Bcl-2, our aim was to evaluate venetoclax as a potential therapy for HCL. We found that clinically relevant concentrations of venetoclax (0.1 and 1 µM) induced primary HCL cell apoptosis in vitro as measured by flow cytometry using Annexin V staining. As microenvironment induces resistance to venetoclax in CLL, we also evaluated its effect in HCL by testing the following stimuli: activated T lymphocytes, stromal cells, TLR-9 agonist CpG, and TLR-2 agonist PAM3. We found decreased levels of venetoclax-induced cytotoxicity in HCL cells exposed for 48 h to any of these stimuli, suggesting that leukemic B cells from HCL patients are sensitive to venetoclax, but this sensitivity can be overcome by signals from the microenvironment. We propose that the combination of venetoclax with drugs that target the microenvironment might improve its efficacy in HCL. Frontiers Media S.A. 2021-07-26 /pmc/articles/PMC8350736/ /pubmed/34381700 http://dx.doi.org/10.3389/fonc.2021.598319 Text en Copyright © 2021 Vereertbrugghen, Colado, Gargiulo, Bezares, Fernández Grecco, Cordini, Custidiano, François, Berchem, Borge, Paggetti, Moussay, Gamberale, Giordano and Morande https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Vereertbrugghen, Alexia
Colado, Ana
Gargiulo, Ernesto
Bezares, Raimundo Fernando
Fernández Grecco, Horacio
Cordini, Gregorio
Custidiano, Maria del Rosario
François, Jean-Hugues
Berchem, Guy
Borge, Mercedes
Paggetti, Jerome
Moussay, Etienne
Gamberale, Romina
Giordano, Mirta
Morande, Pablo Elías
In Vitro Sensitivity to Venetoclax and Microenvironment Protection in Hairy Cell Leukemia
title In Vitro Sensitivity to Venetoclax and Microenvironment Protection in Hairy Cell Leukemia
title_full In Vitro Sensitivity to Venetoclax and Microenvironment Protection in Hairy Cell Leukemia
title_fullStr In Vitro Sensitivity to Venetoclax and Microenvironment Protection in Hairy Cell Leukemia
title_full_unstemmed In Vitro Sensitivity to Venetoclax and Microenvironment Protection in Hairy Cell Leukemia
title_short In Vitro Sensitivity to Venetoclax and Microenvironment Protection in Hairy Cell Leukemia
title_sort in vitro sensitivity to venetoclax and microenvironment protection in hairy cell leukemia
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8350736/
https://www.ncbi.nlm.nih.gov/pubmed/34381700
http://dx.doi.org/10.3389/fonc.2021.598319
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