Blockade of CD73 Increases the Cytotoxic Effects of Fludarabine in Chronic Lymphocytic Leukemia
Background: Ecto-5’-nucleotidase (CD73) is a membrane-bound enzyme that converts adenosine 5’-monophosphate into adenosine. It is proven that the presence of elevated levels of adenosine in the tumor microenvironment induces tumor growth while suppressing immune responses against tumor cells. Accord...
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| Format: | Article |
| Language: | English |
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Tabriz University of Medical Sciences
2022-12-01
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| Series: | ImmunoAnalysis |
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| Online Access: | https://ia.tbzmed.ac.ir/PDF/ia-2-11.pdf |
| _version_ | 1797817514655219712 |
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| author | Mohammad Sadeghi Mahsa Yousefi Bostanabad Omid Abedi Abbas Ali Hosseinpour Feizi Ali Akbar Movasaghpour Akbari Farhad Jadidi-Niaragh |
| author_facet | Mohammad Sadeghi Mahsa Yousefi Bostanabad Omid Abedi Abbas Ali Hosseinpour Feizi Ali Akbar Movasaghpour Akbari Farhad Jadidi-Niaragh |
| author_sort | Mohammad Sadeghi |
| collection | DOAJ |
| description | Background: Ecto-5’-nucleotidase (CD73) is a membrane-bound enzyme that converts adenosine 5’-monophosphate into adenosine. It is proven that the presence of elevated levels of adenosine in the tumor microenvironment induces tumor growth while suppressing immune responses against tumor cells. According to several studies, it is reported that the expression of CD73 is increased in several types of malignancies. In chronic lymphocytic leukemia (CLL), a hematological malignancy characterized by the increased proliferation and accumulation of lymphoid cells in peripheral blood (PB) and lymphoid tissues, CD73 expression is associated with higher-risk disease. Moreover, it is reported that CD73 may contribute to fludarabine (a chemotherapeutic widely used for the treatment of CLL) resistance as well. Methods: We separated mononuclear cells obtained from PB and bone marrow (BM) from eleven CLL patients. Cells were treated individually or in combination with fludarabine and anti-CD73 siRNA (transfection by lipofectamine), and the effect of treatment on cell survival was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test. Results: We found that the highest level of apoptosis induction was observed in cells treated with fludarabine combined with CD73 inhibition, compared to the untreated (P<0.01). Our findings are in support of a study reporting the association between CD73 overactivation and fludarabine resistance. Conclusion: These findings suggest that CD73 inhibition can be a potential target for CLL treatment and can help overcome endurance towards fludarabine and can better the prognosis of CLL-affected individuals. |
| first_indexed | 2024-03-13T08:54:35Z |
| format | Article |
| id | doaj.art-ad90a90c8f8f46279d102a9ffcb33a95 |
| institution | Directory Open Access Journal |
| issn | 2783-2589 |
| language | English |
| last_indexed | 2024-03-13T08:54:35Z |
| publishDate | 2022-12-01 |
| publisher | Tabriz University of Medical Sciences |
| record_format | Article |
| series | ImmunoAnalysis |
| spelling | doaj.art-ad90a90c8f8f46279d102a9ffcb33a952023-05-29T05:17:42ZengTabriz University of Medical SciencesImmunoAnalysis2783-25892022-12-0121111110.34172/ia.2022.11ia-3024Blockade of CD73 Increases the Cytotoxic Effects of Fludarabine in Chronic Lymphocytic LeukemiaMohammad Sadeghi0Mahsa Yousefi Bostanabad1Omid Abedi2Abbas Ali Hosseinpour Feizi3Ali Akbar Movasaghpour Akbari4Farhad Jadidi-Niaragh5Hematology and Oncology Research Centre, Tabriz University of Medical Sciences, Tabriz, IranStudent Research Committee, Tabriz University of Medical Sciences, Tabriz, IranImmunology Research Centre, Tabriz University of Medical Sciences, Tabriz, IranHematology and Oncology Research Centre, Tabriz University of Medical Sciences, Tabriz, IranHematology and Oncology Research Centre, Tabriz University of Medical Sciences, Tabriz, IranImmunology Research Centre, Tabriz University of Medical Sciences, Tabriz, IranBackground: Ecto-5’-nucleotidase (CD73) is a membrane-bound enzyme that converts adenosine 5’-monophosphate into adenosine. It is proven that the presence of elevated levels of adenosine in the tumor microenvironment induces tumor growth while suppressing immune responses against tumor cells. According to several studies, it is reported that the expression of CD73 is increased in several types of malignancies. In chronic lymphocytic leukemia (CLL), a hematological malignancy characterized by the increased proliferation and accumulation of lymphoid cells in peripheral blood (PB) and lymphoid tissues, CD73 expression is associated with higher-risk disease. Moreover, it is reported that CD73 may contribute to fludarabine (a chemotherapeutic widely used for the treatment of CLL) resistance as well. Methods: We separated mononuclear cells obtained from PB and bone marrow (BM) from eleven CLL patients. Cells were treated individually or in combination with fludarabine and anti-CD73 siRNA (transfection by lipofectamine), and the effect of treatment on cell survival was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test. Results: We found that the highest level of apoptosis induction was observed in cells treated with fludarabine combined with CD73 inhibition, compared to the untreated (P<0.01). Our findings are in support of a study reporting the association between CD73 overactivation and fludarabine resistance. Conclusion: These findings suggest that CD73 inhibition can be a potential target for CLL treatment and can help overcome endurance towards fludarabine and can better the prognosis of CLL-affected individuals.https://ia.tbzmed.ac.ir/PDF/ia-2-11.pdfcllfludarabinecd73leukemiasirnachemoresistance |
| spellingShingle | Mohammad Sadeghi Mahsa Yousefi Bostanabad Omid Abedi Abbas Ali Hosseinpour Feizi Ali Akbar Movasaghpour Akbari Farhad Jadidi-Niaragh Blockade of CD73 Increases the Cytotoxic Effects of Fludarabine in Chronic Lymphocytic Leukemia ImmunoAnalysis cll fludarabine cd73 leukemia sirna chemoresistance |
| title | Blockade of CD73 Increases the Cytotoxic Effects of Fludarabine in Chronic Lymphocytic Leukemia |
| title_full | Blockade of CD73 Increases the Cytotoxic Effects of Fludarabine in Chronic Lymphocytic Leukemia |
| title_fullStr | Blockade of CD73 Increases the Cytotoxic Effects of Fludarabine in Chronic Lymphocytic Leukemia |
| title_full_unstemmed | Blockade of CD73 Increases the Cytotoxic Effects of Fludarabine in Chronic Lymphocytic Leukemia |
| title_short | Blockade of CD73 Increases the Cytotoxic Effects of Fludarabine in Chronic Lymphocytic Leukemia |
| title_sort | blockade of cd73 increases the cytotoxic effects of fludarabine in chronic lymphocytic leukemia |
| topic | cll fludarabine cd73 leukemia sirna chemoresistance |
| url | https://ia.tbzmed.ac.ir/PDF/ia-2-11.pdf |
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