Effects of ibrutinib and venetoclax on the expression of immune checkpoint molecules in leukemic blasts of patients with acute lymphoblastic leukemia
Background: In recent decades, targeted therapy using small molecule inhibitors (SMI) have been shown very promising results in the treatment of a variety of solid and hematopoietic malignancies. However, their exact mechanisms, especiallay on the evasion strategies of tumor cells from the host immu...
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Elsevier
2025-06-01
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| Series: | Biochemistry and Biophysics Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405580825001323 |
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| author | Armin Dozandeh-Jouybari Fatemeh Mousavi-Mirkalaei Saeid Taghiloo Hossein Karami Mohammad Naderisorki Ehsan Zaboli Mohammad Eslami-Jouybari Tohid Kazemi Hossein Asgarian-Omran |
| author_facet | Armin Dozandeh-Jouybari Fatemeh Mousavi-Mirkalaei Saeid Taghiloo Hossein Karami Mohammad Naderisorki Ehsan Zaboli Mohammad Eslami-Jouybari Tohid Kazemi Hossein Asgarian-Omran |
| author_sort | Armin Dozandeh-Jouybari |
| collection | DOAJ |
| description | Background: In recent decades, targeted therapy using small molecule inhibitors (SMI) have been shown very promising results in the treatment of a variety of solid and hematopoietic malignancies. However, their exact mechanisms, especiallay on the evasion strategies of tumor cells from the host immune system are not fully understood. The current study investigates the effects of two SMIs, ibrutinib and venetoclax, on the expression of inhibitory immune checkpoint molecules in patients with acute lymphoblastic leukemia (ALL). Methods: Leukemic cells were isolated from 20 patients with ALL by magnetic activated cell sorting (MACS) technique. Isolated leukemic cells were cultured and treated by ibrutinib and venetoclax for 48 h. Cell viability and apoptosis were monitored through MTT and flow cytometry assays, respectively. The mRNA expression levels of checkpoint molecules PD-L1, galectin-9, CD200, CD155, CD47, and anti-inflammatory cytokine TGF-β were determined by Real-Time PCR method. Results: The purity of MACS-isolated ALL leukemic cells was >98% as determined by flow cytometry. Following treatment, the proliferation of leukemic cells was significantly decreased and the apoptosis rate was significantly increased, which was more remarkable for venetoclax. Moreover, treatment of leukemic cells with ibrutinib and venetoclax showed alterations in the mRNA expression of immune checkpoint inhibitory ligands and TGF-β. Conclusion: Our results indicated that small molecule inhibitors not only hinder proliferation and enhance apoptosis, but also affect the expression of inhibitory immune checkpoint ligands. By elucidating the precise underlying mechanisms, these drugs could emerge as promising therapeutic options, particularly in the context of combination therapy for ALL. |
| format | Article |
| id | doaj-art-a2ded3c9990b4f23875050d14fa99e05 |
| institution | OA Journals |
| issn | 2405-5808 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biochemistry and Biophysics Reports |
| spelling | doaj-art-a2ded3c9990b4f23875050d14fa99e052025-08-20T02:17:09ZengElsevierBiochemistry and Biophysics Reports2405-58082025-06-014210204510.1016/j.bbrep.2025.102045Effects of ibrutinib and venetoclax on the expression of immune checkpoint molecules in leukemic blasts of patients with acute lymphoblastic leukemiaArmin Dozandeh-Jouybari0Fatemeh Mousavi-Mirkalaei1Saeid Taghiloo2Hossein Karami3Mohammad Naderisorki4Ehsan Zaboli5Mohammad Eslami-Jouybari6Tohid Kazemi7Hossein Asgarian-Omran8Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran; Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, IranDepartment of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, IranDepartment of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, IranThalassemia Research Center (TRC), Hemoglobinopathy Institute, Mazandaran University of Medical Sciences, Sari, IranThalassemia Research Center (TRC), Hemoglobinopathy Institute, Mazandaran University of Medical Sciences, Sari, IranGastrointestinal Cancer Research Center, Non-Communicable Diseases Institute, Mazandaran University of Medical Sciences, Sari, Iran; Department of Hematology and Oncology, Imam Khomeini Hospital, Mazandaran University of Medical Science, Sari, IranGastrointestinal Cancer Research Center, Non-Communicable Diseases Institute, Mazandaran University of Medical Sciences, Sari, Iran; Department of Hematology and Oncology, Imam Khomeini Hospital, Mazandaran University of Medical Science, Sari, IranImmunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran; Corresponding author. Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran; Gastrointestinal Cancer Research Center, Non-Communicable Diseases Institute, Mazandaran University of Medical Sciences, Sari, Iran; Corresponding author. Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.Background: In recent decades, targeted therapy using small molecule inhibitors (SMI) have been shown very promising results in the treatment of a variety of solid and hematopoietic malignancies. However, their exact mechanisms, especiallay on the evasion strategies of tumor cells from the host immune system are not fully understood. The current study investigates the effects of two SMIs, ibrutinib and venetoclax, on the expression of inhibitory immune checkpoint molecules in patients with acute lymphoblastic leukemia (ALL). Methods: Leukemic cells were isolated from 20 patients with ALL by magnetic activated cell sorting (MACS) technique. Isolated leukemic cells were cultured and treated by ibrutinib and venetoclax for 48 h. Cell viability and apoptosis were monitored through MTT and flow cytometry assays, respectively. The mRNA expression levels of checkpoint molecules PD-L1, galectin-9, CD200, CD155, CD47, and anti-inflammatory cytokine TGF-β were determined by Real-Time PCR method. Results: The purity of MACS-isolated ALL leukemic cells was >98% as determined by flow cytometry. Following treatment, the proliferation of leukemic cells was significantly decreased and the apoptosis rate was significantly increased, which was more remarkable for venetoclax. Moreover, treatment of leukemic cells with ibrutinib and venetoclax showed alterations in the mRNA expression of immune checkpoint inhibitory ligands and TGF-β. Conclusion: Our results indicated that small molecule inhibitors not only hinder proliferation and enhance apoptosis, but also affect the expression of inhibitory immune checkpoint ligands. By elucidating the precise underlying mechanisms, these drugs could emerge as promising therapeutic options, particularly in the context of combination therapy for ALL.http://www.sciencedirect.com/science/article/pii/S2405580825001323ALLIbrutinibVenetoclaxImmune checkpoint moleculesTGF-β |
| spellingShingle | Armin Dozandeh-Jouybari Fatemeh Mousavi-Mirkalaei Saeid Taghiloo Hossein Karami Mohammad Naderisorki Ehsan Zaboli Mohammad Eslami-Jouybari Tohid Kazemi Hossein Asgarian-Omran Effects of ibrutinib and venetoclax on the expression of immune checkpoint molecules in leukemic blasts of patients with acute lymphoblastic leukemia Biochemistry and Biophysics Reports ALL Ibrutinib Venetoclax Immune checkpoint molecules TGF-β |
| title | Effects of ibrutinib and venetoclax on the expression of immune checkpoint molecules in leukemic blasts of patients with acute lymphoblastic leukemia |
| title_full | Effects of ibrutinib and venetoclax on the expression of immune checkpoint molecules in leukemic blasts of patients with acute lymphoblastic leukemia |
| title_fullStr | Effects of ibrutinib and venetoclax on the expression of immune checkpoint molecules in leukemic blasts of patients with acute lymphoblastic leukemia |
| title_full_unstemmed | Effects of ibrutinib and venetoclax on the expression of immune checkpoint molecules in leukemic blasts of patients with acute lymphoblastic leukemia |
| title_short | Effects of ibrutinib and venetoclax on the expression of immune checkpoint molecules in leukemic blasts of patients with acute lymphoblastic leukemia |
| title_sort | effects of ibrutinib and venetoclax on the expression of immune checkpoint molecules in leukemic blasts of patients with acute lymphoblastic leukemia |
| topic | ALL Ibrutinib Venetoclax Immune checkpoint molecules TGF-β |
| url | http://www.sciencedirect.com/science/article/pii/S2405580825001323 |
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