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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Format: | Article |
Language: | English |
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Frontiers Media S.A.
2021-07-01
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Series: | Frontiers in Oncology |
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Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2021.598319/full |
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Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Alexia Vereertbrugghen Ana Colado Ernesto Gargiulo Raimundo Fernando Bezares Horacio Fernández Grecco Gregorio Cordini Gregorio Cordini Maria del Rosario Custidiano Jean-Hugues François Guy Berchem Guy Berchem Mercedes Borge Mercedes Borge Jerome Paggetti Etienne Moussay Romina Gamberale Romina Gamberale Mirta Giordano Mirta Giordano Pablo Elías Morande Pablo Elías Morande |
spellingShingle |
Alexia Vereertbrugghen Ana Colado Ernesto Gargiulo Raimundo Fernando Bezares Horacio Fernández Grecco Gregorio Cordini Gregorio Cordini Maria del Rosario Custidiano Jean-Hugues François Guy Berchem Guy Berchem Mercedes Borge Mercedes Borge Jerome Paggetti Etienne Moussay Romina Gamberale Romina Gamberale Mirta Giordano Mirta Giordano Pablo Elías Morande Pablo Elías Morande In Vitro Sensitivity to Venetoclax and Microenvironment Protection in Hairy Cell Leukemia Frontiers in Oncology hairy cell leukemia ABT-199 cell death leukemia microenvironment venetoclax |
author_facet |
Alexia Vereertbrugghen Ana Colado Ernesto Gargiulo Raimundo Fernando Bezares Horacio Fernández Grecco Gregorio Cordini Gregorio Cordini Maria del Rosario Custidiano Jean-Hugues François Guy Berchem Guy Berchem Mercedes Borge Mercedes Borge Jerome Paggetti Etienne Moussay Romina Gamberale Romina Gamberale Mirta Giordano Mirta Giordano Pablo Elías Morande Pablo Elías Morande |
author_sort |
Alexia Vereertbrugghen |
title |
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_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_sort |
in vitro sensitivity to venetoclax and microenvironment protection in hairy cell leukemia |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Oncology |
issn |
2234-943X |
publishDate |
2021-07-01 |
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. |
topic |
hairy cell leukemia ABT-199 cell death leukemia microenvironment venetoclax |
url |
https://www.frontiersin.org/articles/10.3389/fonc.2021.598319/full |
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doaj-8023bcc1246e4bd080357aa16d54a4d12021-07-26T13:48:34ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-07-011110.3389/fonc.2021.598319598319In Vitro Sensitivity to Venetoclax and Microenvironment Protection in Hairy Cell LeukemiaAlexia Vereertbrugghen0Ana Colado1Ernesto Gargiulo2Raimundo Fernando Bezares3Horacio Fernández Grecco4Gregorio Cordini5Gregorio Cordini6Maria del Rosario Custidiano7Jean-Hugues François8Guy Berchem9Guy Berchem10Mercedes Borge11Mercedes Borge12Jerome Paggetti13Etienne Moussay14Romina Gamberale15Romina Gamberale16Mirta Giordano17Mirta Giordano18Pablo Elías Morande19Pablo Elías Morande20Instituto de Medicina Experimental (IMEX)–CONICET–Academia Nacional de Medicina (ANM), Buenos Aires, ArgentinaInstituto de Medicina Experimental (IMEX)–CONICET–Academia Nacional de Medicina (ANM), Buenos Aires, ArgentinaTumor Stroma Interactions, Department of Oncology, Luxembourg Institute of Health, Luxembourg, LuxembourgSección Hematología, Hospital General de Agudos Dr. Teodoro Álvarez, Buenos Aires, ArgentinaSección Hematología, Sanatorio Municipal Dr. Julio Méndez, Buenos Aires, ArgentinaInstituto de Medicina Experimental (IMEX)–CONICET–Academia Nacional de Medicina (ANM), Buenos Aires, ArgentinaHospital de Clínicas José de San Martín, Universidad de Buenos Aires, Buenos Aires, ArgentinaServicio de Hematología y Transplante de Médula Ósea, Instituto Alexander Fleming, Buenos Aires, ArgentinaLaboratory of Hematology, Centre Hospitalier de Luxembourg, Luxembourg, LuxembourgTumor Stroma Interactions, Department of Oncology, Luxembourg Institute of Health, Luxembourg, LuxembourgDepartment of Hemato-Oncology, Centre Hospitalier de Luxembourg, Luxembourg, LuxembourgInstituto de Medicina Experimental (IMEX)–CONICET–Academia Nacional de Medicina (ANM), Buenos Aires, ArgentinaDepartamento de Microbiología, Parasitología e Inmunología, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, ArgentinaTumor Stroma Interactions, Department of Oncology, Luxembourg Institute of Health, Luxembourg, LuxembourgTumor Stroma Interactions, Department of Oncology, Luxembourg Institute of Health, Luxembourg, LuxembourgInstituto de Medicina Experimental (IMEX)–CONICET–Academia Nacional de Medicina (ANM), Buenos Aires, ArgentinaDepartamento de Microbiología, Parasitología e Inmunología, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, ArgentinaInstituto de Medicina Experimental (IMEX)–CONICET–Academia Nacional de Medicina (ANM), Buenos Aires, ArgentinaDepartamento de Microbiología, Parasitología e Inmunología, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, ArgentinaInstituto de Medicina Experimental (IMEX)–CONICET–Academia Nacional de Medicina (ANM), Buenos Aires, ArgentinaTumor Stroma Interactions, Department of Oncology, Luxembourg Institute of Health, Luxembourg, LuxembourgCurrent 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.https://www.frontiersin.org/articles/10.3389/fonc.2021.598319/fullhairy cell leukemiaABT-199cell deathleukemia microenvironmentvenetoclax |