Potassium/sodium cation carriers robustly up-regulate CD20 antigen by targeting MYC, and synergize with anti-CD20 immunotherapies to eliminate malignant B cells
Our investigation uncovers that nanomolar concentrations of salinomycin, monensin, nigericin, and narasin (a group of potassium/sodium cation carriers) robustly enhance surface expression of CD20 antigen in B-cell-derived tumor cells, including primary malignant cells of chronic lymphocytic leukemi...
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| Format: | Article |
| Language: | English |
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Ferrata Storti Foundation
2024-12-01
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| Series: | Haematologica |
| Online Access: | https://haematologica.org/article/view/11877 |
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| author | Anna Torun Aleksandra Zdanowicz Nina Miazek-Zapala Piotr Zapala Bhaskar Pradhan Marta Jedrzejczyk Andrzej Ciechanowicz Zofia Pilch Marcin Skorzynski Mikołaj Słabicki Grzegorz Rymkiewicz Joanna Barankiewicz Claudio Martines Luca Laurenti Marta Struga Magdalena Winiarska Jakub Golab Magdalena Kucia Mariusz Z. Ratajczak Adam Huczynski Dinis P. Calado Dimitar G. Efremov Abdessamad Zerrouqi Beata Pyrzynska |
| author_facet | Anna Torun Aleksandra Zdanowicz Nina Miazek-Zapala Piotr Zapala Bhaskar Pradhan Marta Jedrzejczyk Andrzej Ciechanowicz Zofia Pilch Marcin Skorzynski Mikołaj Słabicki Grzegorz Rymkiewicz Joanna Barankiewicz Claudio Martines Luca Laurenti Marta Struga Magdalena Winiarska Jakub Golab Magdalena Kucia Mariusz Z. Ratajczak Adam Huczynski Dinis P. Calado Dimitar G. Efremov Abdessamad Zerrouqi Beata Pyrzynska |
| author_sort | Anna Torun |
| collection | DOAJ |
| description |
Our investigation uncovers that nanomolar concentrations of salinomycin, monensin, nigericin, and narasin (a group of potassium/sodium cation carriers) robustly enhance surface expression of CD20 antigen in B-cell-derived tumor cells, including primary malignant cells of chronic lymphocytic leukemia and diffuse large B-cell lymphoma. Experiments in vitro, ex vivo, and animal model reveal a novel approach of combining salinomycin or monensin with therapeutic anti-CD20 monoclonal antibodies or anti-CD20 CAR-T cells, significantly improving non- Hodgkin lymphoma (NHL) therapy. The results of RNA-seq, genetic editing, and chemical inhibition delineate the molecular mechanism of CD20 upregulation, at least partially, to the downregulation of MYC, the transcriptional repressor of the MS4A1 gene encoding CD20. Our findings propose the cation carriers as compounds targeting MYC oncogene, which can be combined with anti-CD20 antibodies or adoptive cellular therapies to treat NHL and mitigate resistance, which frequently depends on the CD20 antigen loss, offering new solutions to improve patient outcomes.
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| format | Article |
| id | doaj-art-76b782877c9b4f9ebf19e99dbbf87ecd |
| institution | Kabale University |
| issn | 0390-6078 1592-8721 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Ferrata Storti Foundation |
| record_format | Article |
| series | Haematologica |
| spelling | doaj-art-76b782877c9b4f9ebf19e99dbbf87ecd2024-12-19T19:43:17ZengFerrata Storti FoundationHaematologica0390-60781592-87212024-12-01999110.3324/haematol.2024.285826Potassium/sodium cation carriers robustly up-regulate CD20 antigen by targeting MYC, and synergize with anti-CD20 immunotherapies to eliminate malignant B cellsAnna Torun0Aleksandra Zdanowicz1Nina Miazek-Zapala2Piotr Zapala3Bhaskar Pradhan4Marta Jedrzejczyk5Andrzej Ciechanowicz6Zofia Pilch7Marcin Skorzynski8Mikołaj Słabicki9Grzegorz Rymkiewicz10Joanna Barankiewicz11Claudio Martines12Luca Laurenti13Marta Struga14Magdalena Winiarska15Jakub Golab16Magdalena Kucia17Mariusz Z. Ratajczak18Adam Huczynski19Dinis P. Calado20Dimitar G. Efremov21Abdessamad Zerrouqi22Beata Pyrzynska23Medical University of Warsaw, WarsawMedical University of Warsaw, Warsaw, Poland; Doctoral School, Medical University of Warsaw, WarsawMedical University of Warsaw, WarsawMedical University of Warsaw, WarsawMedical University of Warsaw, Warsaw, Poland; Doctoral School, Medical University of Warsaw, WarsawAdam Mickiewicz University, PoznanMedical University of Warsaw, WarsawMedical University of Warsaw, WarsawMedical University of Warsaw, WarsawBroad Institute of MIT and Harvard, Cambridge, MA, USA; Dana-Farber Cancer Institute, Boston, MA, USAMaria Sklodowska-Curie National Research Institute of Oncology, WarsawInstitute of Hematology and Transfusion Medicine, WarsawMolecular Hematology Unit, International Centre for Genetic Engineering and Biotechnology, TriesteHematology Unit, Fundazione Policlinico Universitario A Gemelli IRCCS, RomeMedical University of Warsaw, WarsawMedical University of Warsaw, WarsawMedical University of Warsaw, WarsawMedical University of Warsaw, WarsawMedical University of Warsaw, WarsawAdam Mickiewicz University, PoznanThe Francis Crick Institute, London, United KingdomMolecular Hematology Unit, International Centre for Genetic Engineering and Biotechnology, TriesteMedical University of Warsaw, Warsaw, Poland; Senior authorsMedical University of Warsaw, Warsaw, Poland; Senior authors Our investigation uncovers that nanomolar concentrations of salinomycin, monensin, nigericin, and narasin (a group of potassium/sodium cation carriers) robustly enhance surface expression of CD20 antigen in B-cell-derived tumor cells, including primary malignant cells of chronic lymphocytic leukemia and diffuse large B-cell lymphoma. Experiments in vitro, ex vivo, and animal model reveal a novel approach of combining salinomycin or monensin with therapeutic anti-CD20 monoclonal antibodies or anti-CD20 CAR-T cells, significantly improving non- Hodgkin lymphoma (NHL) therapy. The results of RNA-seq, genetic editing, and chemical inhibition delineate the molecular mechanism of CD20 upregulation, at least partially, to the downregulation of MYC, the transcriptional repressor of the MS4A1 gene encoding CD20. Our findings propose the cation carriers as compounds targeting MYC oncogene, which can be combined with anti-CD20 antibodies or adoptive cellular therapies to treat NHL and mitigate resistance, which frequently depends on the CD20 antigen loss, offering new solutions to improve patient outcomes. https://haematologica.org/article/view/11877 |
| spellingShingle | Anna Torun Aleksandra Zdanowicz Nina Miazek-Zapala Piotr Zapala Bhaskar Pradhan Marta Jedrzejczyk Andrzej Ciechanowicz Zofia Pilch Marcin Skorzynski Mikołaj Słabicki Grzegorz Rymkiewicz Joanna Barankiewicz Claudio Martines Luca Laurenti Marta Struga Magdalena Winiarska Jakub Golab Magdalena Kucia Mariusz Z. Ratajczak Adam Huczynski Dinis P. Calado Dimitar G. Efremov Abdessamad Zerrouqi Beata Pyrzynska Potassium/sodium cation carriers robustly up-regulate CD20 antigen by targeting MYC, and synergize with anti-CD20 immunotherapies to eliminate malignant B cells Haematologica |
| title | Potassium/sodium cation carriers robustly up-regulate CD20 antigen by targeting MYC, and synergize with anti-CD20 immunotherapies to eliminate malignant B cells |
| title_full | Potassium/sodium cation carriers robustly up-regulate CD20 antigen by targeting MYC, and synergize with anti-CD20 immunotherapies to eliminate malignant B cells |
| title_fullStr | Potassium/sodium cation carriers robustly up-regulate CD20 antigen by targeting MYC, and synergize with anti-CD20 immunotherapies to eliminate malignant B cells |
| title_full_unstemmed | Potassium/sodium cation carriers robustly up-regulate CD20 antigen by targeting MYC, and synergize with anti-CD20 immunotherapies to eliminate malignant B cells |
| title_short | Potassium/sodium cation carriers robustly up-regulate CD20 antigen by targeting MYC, and synergize with anti-CD20 immunotherapies to eliminate malignant B cells |
| title_sort | potassium sodium cation carriers robustly up regulate cd20 antigen by targeting myc and synergize with anti cd20 immunotherapies to eliminate malignant b cells |
| url | https://haematologica.org/article/view/11877 |
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