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49 results on '"Leon, Leticia G."'

2. The tumor suppressor MIR139 is silenced by POLR2M to promote AML oncogenesis

Author

Stavast, Christiaan J., van Zuijen, Iris, Karkoulia, Elena, Özçelik, Arman, van Hoven-Beijen, Antoinette, Leon, Leticia G., Voerman, Jane S. A., Janssen, George M. C., van Veelen, Peter A., Burocziova, Monika, Brouwer, Rutger W. W., van IJcken, Wilfred F. J., Maas, Alex, Bindels, Eric M., van der Velden, Vincent H. J., Schliehe, Christopher, Katsikis, Peter D., Alberich-Jorda, Meritxell, and Erkeland, Stefan J.

Published
2022
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3. TABLE 3 from Risk Prediction of Metachronous Colorectal Cancer from Molecular Features of Adenomas: A Nested Case–Control Study

Author

Jodal, Henriette C., primary, Akwiwu, Eddymurphy U., primary, Lemmens, Margriet, primary, Delis-van Diemen, Pien M., primary, Klotz, Dagmar, primary, Leon, Leticia G., primary, Lakbir, Soufyan, primary, de Wit, Meike, primary, Fijneman, Remond J.A., primary, van Leerdam, Monique E., primary, Dekker, Evelien, primary, Spaander, Manon C.W., primary, Meijer, Gerrit A., primary, Løberg, Magnus, primary, Coupé, Veerle M.H., primary, Kalager, Mette, primary, and Carvalho, Beatriz, primary

Published
2023
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4. TABLE 4 from Risk Prediction of Metachronous Colorectal Cancer from Molecular Features of Adenomas: A Nested Case–Control Study

Author

Jodal, Henriette C., primary, Akwiwu, Eddymurphy U., primary, Lemmens, Margriet, primary, Delis-van Diemen, Pien M., primary, Klotz, Dagmar, primary, Leon, Leticia G., primary, Lakbir, Soufyan, primary, de Wit, Meike, primary, Fijneman, Remond J.A., primary, van Leerdam, Monique E., primary, Dekker, Evelien, primary, Spaander, Manon C.W., primary, Meijer, Gerrit A., primary, Løberg, Magnus, primary, Coupé, Veerle M.H., primary, Kalager, Mette, primary, and Carvalho, Beatriz, primary

Published
2023
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5. FIGURE 1 from Risk Prediction of Metachronous Colorectal Cancer from Molecular Features of Adenomas: A Nested Case–Control Study

Author

Jodal, Henriette C., primary, Akwiwu, Eddymurphy U., primary, Lemmens, Margriet, primary, Delis-van Diemen, Pien M., primary, Klotz, Dagmar, primary, Leon, Leticia G., primary, Lakbir, Soufyan, primary, de Wit, Meike, primary, Fijneman, Remond J.A., primary, van Leerdam, Monique E., primary, Dekker, Evelien, primary, Spaander, Manon C.W., primary, Meijer, Gerrit A., primary, Løberg, Magnus, primary, Coupé, Veerle M.H., primary, Kalager, Mette, primary, and Carvalho, Beatriz, primary

Published
2023
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6. Supplementary Figure 1 from Risk Prediction of Metachronous Colorectal Cancer from Molecular Features of Adenomas: A Nested Case–Control Study

Author

Jodal, Henriette C., primary, Akwiwu, Eddymurphy U., primary, Lemmens, Margriet, primary, Delis-van Diemen, Pien M., primary, Klotz, Dagmar, primary, Leon, Leticia G., primary, Lakbir, Soufyan, primary, de Wit, Meike, primary, Fijneman, Remond J.A., primary, van Leerdam, Monique E., primary, Dekker, Evelien, primary, Spaander, Manon C.W., primary, Meijer, Gerrit A., primary, Løberg, Magnus, primary, Coupé, Veerle M.H., primary, Kalager, Mette, primary, and Carvalho, Beatriz, primary

Published
2023
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7. TABLE 7 from Risk Prediction of Metachronous Colorectal Cancer from Molecular Features of Adenomas: A Nested Case–Control Study

Author

Jodal, Henriette C., primary, Akwiwu, Eddymurphy U., primary, Lemmens, Margriet, primary, Delis-van Diemen, Pien M., primary, Klotz, Dagmar, primary, Leon, Leticia G., primary, Lakbir, Soufyan, primary, de Wit, Meike, primary, Fijneman, Remond J.A., primary, van Leerdam, Monique E., primary, Dekker, Evelien, primary, Spaander, Manon C.W., primary, Meijer, Gerrit A., primary, Løberg, Magnus, primary, Coupé, Veerle M.H., primary, Kalager, Mette, primary, and Carvalho, Beatriz, primary

Published
2023
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8. Risk Prediction of Metachronous Colorectal Cancer from Molecular Features of Adenomas: A Nested Case–Control Study

Author

Jodal, Henriette C., primary, Akwiwu, Eddymurphy U., additional, Lemmens, Margriet, additional, Delis-van Diemen, Pien M., additional, Klotz, Dagmar, additional, Leon, Leticia G., additional, Lakbir, Soufyan, additional, de Wit, Meike, additional, Fijneman, Remond J.A., additional, van Leerdam, Monique E., additional, Dekker, Evelien, additional, Spaander, Manon C.W., additional, Meijer, Gerrit A., additional, Løberg, Magnus, additional, Coupé, Veerle M.H., additional, Kalager, Mette, additional, and Carvalho, Beatriz, additional

Published
2023
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9. TABLE 5 from Risk Prediction of Metachronous Colorectal Cancer from Molecular Features of Adenomas: A Nested Case–Control Study

Author

Jodal, Henriette C., primary, Akwiwu, Eddymurphy U., primary, Lemmens, Margriet, primary, Delis-van Diemen, Pien M., primary, Klotz, Dagmar, primary, Leon, Leticia G., primary, Lakbir, Soufyan, primary, de Wit, Meike, primary, Fijneman, Remond J.A., primary, van Leerdam, Monique E., primary, Dekker, Evelien, primary, Spaander, Manon C.W., primary, Meijer, Gerrit A., primary, Løberg, Magnus, primary, Coupé, Veerle M.H., primary, Kalager, Mette, primary, and Carvalho, Beatriz, primary

Published
2023
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10. Supplementary Figure 2 from Risk Prediction of Metachronous Colorectal Cancer from Molecular Features of Adenomas: A Nested Case–Control Study

Author

Jodal, Henriette C., primary, Akwiwu, Eddymurphy U., primary, Lemmens, Margriet, primary, Delis-van Diemen, Pien M., primary, Klotz, Dagmar, primary, Leon, Leticia G., primary, Lakbir, Soufyan, primary, de Wit, Meike, primary, Fijneman, Remond J.A., primary, van Leerdam, Monique E., primary, Dekker, Evelien, primary, Spaander, Manon C.W., primary, Meijer, Gerrit A., primary, Løberg, Magnus, primary, Coupé, Veerle M.H., primary, Kalager, Mette, primary, and Carvalho, Beatriz, primary

Published
2023
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11. TABLE 6 from Risk Prediction of Metachronous Colorectal Cancer from Molecular Features of Adenomas: A Nested Case–Control Study

Author

Jodal, Henriette C., primary, Akwiwu, Eddymurphy U., primary, Lemmens, Margriet, primary, Delis-van Diemen, Pien M., primary, Klotz, Dagmar, primary, Leon, Leticia G., primary, Lakbir, Soufyan, primary, de Wit, Meike, primary, Fijneman, Remond J.A., primary, van Leerdam, Monique E., primary, Dekker, Evelien, primary, Spaander, Manon C.W., primary, Meijer, Gerrit A., primary, Løberg, Magnus, primary, Coupé, Veerle M.H., primary, Kalager, Mette, primary, and Carvalho, Beatriz, primary

Published
2023
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12. Data from Risk Prediction of Metachronous Colorectal Cancer from Molecular Features of Adenomas: A Nested Case–Control Study

Author

Jodal, Henriette C., primary, Akwiwu, Eddymurphy U., primary, Lemmens, Margriet, primary, Delis-van Diemen, Pien M., primary, Klotz, Dagmar, primary, Leon, Leticia G., primary, Lakbir, Soufyan, primary, de Wit, Meike, primary, Fijneman, Remond J.A., primary, van Leerdam, Monique E., primary, Dekker, Evelien, primary, Spaander, Manon C.W., primary, Meijer, Gerrit A., primary, Løberg, Magnus, primary, Coupé, Veerle M.H., primary, Kalager, Mette, primary, and Carvalho, Beatriz, primary

Published
2023
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13. FIGURE 2 from Risk Prediction of Metachronous Colorectal Cancer from Molecular Features of Adenomas: A Nested Case–Control Study

Author

Jodal, Henriette C., primary, Akwiwu, Eddymurphy U., primary, Lemmens, Margriet, primary, Delis-van Diemen, Pien M., primary, Klotz, Dagmar, primary, Leon, Leticia G., primary, Lakbir, Soufyan, primary, de Wit, Meike, primary, Fijneman, Remond J.A., primary, van Leerdam, Monique E., primary, Dekker, Evelien, primary, Spaander, Manon C.W., primary, Meijer, Gerrit A., primary, Løberg, Magnus, primary, Coupé, Veerle M.H., primary, Kalager, Mette, primary, and Carvalho, Beatriz, primary

Published
2023
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14. TABLE 2 from Risk Prediction of Metachronous Colorectal Cancer from Molecular Features of Adenomas: A Nested Case–Control Study

Author

Jodal, Henriette C., primary, Akwiwu, Eddymurphy U., primary, Lemmens, Margriet, primary, Delis-van Diemen, Pien M., primary, Klotz, Dagmar, primary, Leon, Leticia G., primary, Lakbir, Soufyan, primary, de Wit, Meike, primary, Fijneman, Remond J.A., primary, van Leerdam, Monique E., primary, Dekker, Evelien, primary, Spaander, Manon C.W., primary, Meijer, Gerrit A., primary, Løberg, Magnus, primary, Coupé, Veerle M.H., primary, Kalager, Mette, primary, and Carvalho, Beatriz, primary

Published
2023
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15. TABLE 1 from Risk Prediction of Metachronous Colorectal Cancer from Molecular Features of Adenomas: A Nested Case–Control Study

Author

Jodal, Henriette C., primary, Akwiwu, Eddymurphy U., primary, Lemmens, Margriet, primary, Delis-van Diemen, Pien M., primary, Klotz, Dagmar, primary, Leon, Leticia G., primary, Lakbir, Soufyan, primary, de Wit, Meike, primary, Fijneman, Remond J.A., primary, van Leerdam, Monique E., primary, Dekker, Evelien, primary, Spaander, Manon C.W., primary, Meijer, Gerrit A., primary, Løberg, Magnus, primary, Coupé, Veerle M.H., primary, Kalager, Mette, primary, and Carvalho, Beatriz, primary

Published
2023
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17. Supplementary Methods from MicroRNA-21 in Pancreatic Cancer: Correlation with Clinical Outcome and Pharmacologic Aspects Underlying Its Role in the Modulation of Gemcitabine Activity

Author

Giovannetti, Elisa, primary, Funel, Niccola, primary, Peters, Godefridus J., primary, Del Chiaro, Marco, primary, Erozenci, Leyla A., primary, Vasile, Enrico, primary, Leon, Leticia G., primary, Pollina, Luca E., primary, Groen, Annemieke, primary, Falcone, Alfredo, primary, Danesi, Romano, primary, Campani, Daniela, primary, Verheul, Henk M., primary, and Boggi, Ugo, primary

Published
2023
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18. Supplementary Figures 1-5 from MicroRNA-21 in Pancreatic Cancer: Correlation with Clinical Outcome and Pharmacologic Aspects Underlying Its Role in the Modulation of Gemcitabine Activity

Author

Giovannetti, Elisa, primary, Funel, Niccola, primary, Peters, Godefridus J., primary, Del Chiaro, Marco, primary, Erozenci, Leyla A., primary, Vasile, Enrico, primary, Leon, Leticia G., primary, Pollina, Luca E., primary, Groen, Annemieke, primary, Falcone, Alfredo, primary, Danesi, Romano, primary, Campani, Daniela, primary, Verheul, Henk M., primary, and Boggi, Ugo, primary

Published
2023
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19. Data from MicroRNA-21 in Pancreatic Cancer: Correlation with Clinical Outcome and Pharmacologic Aspects Underlying Its Role in the Modulation of Gemcitabine Activity

Author

Giovannetti, Elisa, primary, Funel, Niccola, primary, Peters, Godefridus J., primary, Del Chiaro, Marco, primary, Erozenci, Leyla A., primary, Vasile, Enrico, primary, Leon, Leticia G., primary, Pollina, Luca E., primary, Groen, Annemieke, primary, Falcone, Alfredo, primary, Danesi, Romano, primary, Campani, Daniela, primary, Verheul, Henk M., primary, and Boggi, Ugo, primary

Published
2023
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20. Supplementary Video from MicroRNA-21 in Pancreatic Cancer: Correlation with Clinical Outcome and Pharmacologic Aspects Underlying Its Role in the Modulation of Gemcitabine Activity

Author

Giovannetti, Elisa, primary, Funel, Niccola, primary, Peters, Godefridus J., primary, Del Chiaro, Marco, primary, Erozenci, Leyla A., primary, Vasile, Enrico, primary, Leon, Leticia G., primary, Pollina, Luca E., primary, Groen, Annemieke, primary, Falcone, Alfredo, primary, Danesi, Romano, primary, Campani, Daniela, primary, Verheul, Henk M., primary, and Boggi, Ugo, primary

Published
2023
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21. Abstract A004: Molecular adenoma features to predict metachronous colorectal cancer risk: A nested-case control study

Author

Jodal, Henriette C., primary, Akwiwu, Eddymurphy U., additional, Leon, Leticia G., additional, Lemmens, Margriet, additional, Delis-van Diemen, Pien, additional, Klotz, Dagmar, additional, de Wit, Meike, additional, Fijneman, Remond, additional, van Leerdam, Monique, additional, Dekker, Evelien, additional, Spaander, Manon C. W., additional, Meijer, Gerrit A., additional, Bretthauer, Michael, additional, Løberg, Magnus, additional, Coupé, Veerle M. H., additional, Kalager, Mette, additional, and Carvalho, Beatriz, additional

Published
2022
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23. Transcriptional profiling and biomarker identification reveal tissue specific effects of expanded ataxin-3 in a spinocerebellar ataxia type 3 mouse model

Author

Toonen, Lodewijk J. A., Overzier, Maurice, Evers, Melvin M., Leon, Leticia G., van der Zeeuw, Sander A. J., Mei, Hailiang, Kielbasa, Szymon M., Goeman, Jelle J., Hettne, Kristina M., Magnusson, Olafur Th., Poirel, Marion, Seyer, Alexandre, ‘t Hoen, Peter A. C., and van Roon-Mom, Willeke M. C.

Published
2018
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24. miR-181a is a novel player in the STAT3-mediated survival network of TCRαβ+ CD8+ T large granular lymphocyte leukemia

Author

Assmann, Jorn L. J. C., primary, Leon, Leticia G., additional, Stavast, Christiaan J., additional, van den Bogaerdt, Sanne E., additional, Schilperoord-Vermeulen, Joyce, additional, Sandberg, Yorick, additional, Bellido, Mar, additional, Erkeland, Stefan J., additional, Feith, David J., additional, Loughran Jr, Thomas P., additional, and Langerak, Anton W., additional

Published
2021
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26. The tumor suppressor MIR139 is silenced by POLR2M to promote AML oncogenesis

Author

Stavast, Christiaan J., primary, van Zuijen, Iris, additional, Karkoulia, Elena, additional, Özçelik, Arman, additional, van Hoven-Beijen, Antoinette, additional, Leon, Leticia G., additional, Voerman, Jane S. A., additional, Janssen, George M. C., additional, van Veelen, Peter A., additional, Burocziova, Monika, additional, Brouwer, Rutger W. W., additional, van IJcken, Wilfred F. J., additional, Maas, Alex, additional, Bindels, Eric M., additional, van der Velden, Vincent H. J., additional, Schliehe, Christopher, additional, Katsikis, Peter D., additional, Alberich-Jorda, Meritxell, additional, and Erkeland, Stefan J., additional

Published
2021
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27. The miR-200c/141-ZEB2-TGFβ axis is aberrant in human T-cell prolymphocytic leukemia

Author

Erkeland, Stefan J., primary, Stavast, Christiaan J., additional, Schilperoord-Vermeulen, Joyce, additional, Dal Collo, Giada, additional, Van de Werken, Harmen J.G., additional, Leon, Leticia G., additional, Van Hoven-Beijen, Antoinette, additional, Van Zuijen, Iris, additional, Mueller, Yvonne M., additional, Bindels, Eric M., additional, De Ridder, Dick, additional, Kappers-Klunne, Mies C., additional, Van Lom, Kirsten, additional, Van der Velden, Vincent H.J., additional, and Langerak, Anton W., additional

Published
2021
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29. Rapid in vitro generation of bona fide exhausted CD8+ T cells is accompanied by Tcf7 promotor methylation

Author

Zhao, Manzhi, primary, Kiernan, Caoimhe H., additional, Stairiker, Christopher J., additional, Hope, Jennifer L., additional, Leon, Leticia G., additional, van Meurs, Marjan, additional, Brouwers-Haspels, Inge, additional, Boers, Ruben, additional, Boers, Joachim, additional, Gribnau, Joost, additional, van IJcken, Wilfred F. J., additional, Bindels, Eric M., additional, Hoogenboezem, Remco M., additional, Erkeland, Stefan J., additional, Mueller, Yvonne M., additional, and Katsikis, Peter D., additional

Published
2020
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31. Identification of a core miRNA signature unique to exhausted cytotoxic CD8+ T cells

Author

Kiernan, Caoimhe H., primary, Hope, Jennifer L, additional, Leon, Leticia G., additional, Zhao, Manzhi, additional, van Meurs, Marjan, additional, Brouwers-Haspels, Inge, additional, van Strien, Paulette, additional, Bindels, Erik, additional, Hoogenboezem, Remco M., additional, Li, Yunlei, additional, Stubbs, Andrew P., additional, Zehn, Dietmar, additional, Mueller, Yvonne M, additional, Erkeland, Stefan J., additional, and Katsikis, Peter D, additional

Published
2020
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32. Glucocorticoid Resistant Pediatric Acute Lymphoblastic Leukemia Samples Display Altered Splicing Profile and Vulnerability to Spliceosome Modulation

Author

Sciarrillo, Rocco, primary, Wojtuszkiewicz, Anna, additional, Kooi, Irsan E., additional, Leon, Leticia G., additional, Sonneveld, Edwin, additional, Kuiper, Roland P., additional, Jansen, Gerrit, additional, Giovannetti, Elisa, additional, Kaspers, Gertjan J.L., additional, and Cloos, Jacqueline, additional

Published
2020
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33. Lung transcriptional unresponsiveness and loss of early influenza virus control in infected neonates is prevented by intranasal Lactobacillus rhamnosus GG

Author

Kumova, Ogan K., primary, Fike, Adam J., additional, Thayer, Jillian L., additional, Nguyen, Linda T., additional, Mell, Joshua Chang, additional, Pascasio, Judy, additional, Stairiker, Christopher, additional, Leon, Leticia G., additional, Katsikis, Peter D., additional, and Carey, Alison J., additional

Published
2019
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35. Fatigue in Sjögren's Syndrome: A Search for Biomarkers and Treatment Targets

Author

Bodewes, Iris L. A., primary, van der Spek, Peter J., additional, Leon, Leticia G., additional, Wijkhuijs, Annemarie J. M., additional, van Helden-Meeuwsen, Cornelia G., additional, Tas, Liselotte, additional, Schreurs, Marco W. J., additional, van Daele, Paul L. A., additional, Katsikis, Peter D., additional, and Versnel, Marjan A., additional

Published
2019
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37. The tumor suppressor MIR139is silenced by POLR2M to promote AML oncogenesis

Author

Stavast, Christiaan J., van Zuijen, Iris, Karkoulia, Elena, Özçelik, Arman, van Hoven-Beijen, Antoinette, Leon, Leticia G., Voerman, Jane S. A., Janssen, George M. C., van Veelen, Peter A., Burocziova, Monika, Brouwer, Rutger W. W., van IJcken, Wilfred F. J., Maas, Alex, Bindels, Eric M., van der Velden, Vincent H. J., Schliehe, Christopher, Katsikis, Peter D., Alberich-Jorda, Meritxell, and Erkeland, Stefan J.

Abstract

MIR139is a tumor suppressor and is commonly silenced in acute myeloid leukemia (AML). However, the tumor-suppressing activities of miR-139and molecular mechanisms of MIR139-silencing remain largely unknown. Here, we studied the poorly prognostic MLL-AF9 fusion protein-expressing AML. We show that MLL-AF9 expression in hematopoietic precursors caused epigenetic silencing of MIR139, whereas overexpression of MIR139inhibited in vitro and in vivo AML outgrowth. We identified novel miR-139targets that mediate the tumor-suppressing activities of miR-139in MLL-AF9 AML. We revealed that two enhancer regions control MIR139expression and found that the polycomb repressive complex 2 (PRC2) downstream of MLL-AF9 epigenetically silenced MIR139in AML. Finally, a genome-wide CRISPR-Cas9 knockout screen revealed RNA Polymerase 2 Subunit M (POLR2M) as a novel MIR139-regulatory factor. Our findings elucidate the molecular control of tumor suppressor MIR139and reveal a role for POLR2Min the MIR139-silencing mechanism, downstream of MLL-AF9 and PRC2 in AML. In addition, we confirmed these findings in human AML cell lines with different oncogenic aberrations, suggesting that this is a more common oncogenic mechanism in AML. Our results may pave the way for new targeted therapy in AML.

Published
2021
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41. Phospho-Akt overexpression is prognostic and can be used to tailor the synergistic interaction of Akt inhibitors with gemcitabine in pancreatic cancer

Author

Massihnia, Daniela, primary, Avan, Amir, additional, Funel, Niccola, additional, Maftouh, Mina, additional, van Krieken, Anne, additional, Granchi, Carlotta, additional, Raktoe, Rajiv, additional, Boggi, Ugo, additional, Aicher, Babette, additional, Minutolo, Filippo, additional, Russo, Antonio, additional, Leon, Leticia G., additional, Peters, Godefridus J., additional, and Giovannetti, Elisa, additional

Published
2017
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45. Abstract 4335: Role of proton-coupled folate transporter expression in resistance of mesothelioma patients treated with pemetrexed

Author

Giovannetti, Elisa, primary, Zucali, Paolo A., additional, Assaraf, Yehuda G., additional, Funel, Niccola, additional, Gemelli, Maria, additional, Stark, Michal, additional, Leon, Leticia G., additional, Hou, Zhanjun, additional, Perrino, Matteo, additional, Matherly, Larry H., additional, and Peters, Godefridus J., additional

Published
2015
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46. NF-κB drives acquired resistance to a novel mutant-selective EGFR inhibitor

Author

Galvani, Elena, primary, Sun, Jing, additional, Leon, Leticia G., additional, Sciarrillo, Rocco, additional, Narayan, Ravi S., additional, Tjin Tham Sjin, Robert, additional, Lee, Kwangho, additional, Ohashi, Kadoaki, additional, Heideman, Daniëlle A.M., additional, Alfieri, Roberta R., additional, Heynen, Guus J., additional, Bernards, René, additional, Smit, Egbert F., additional, Pao, William, additional, Peters, Godefridus J., additional, and Giovannetti, Elisa, additional

Published
2015
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47. Development of bioluminescent chick chorioallantoic membrane (CAM) models for primary pancreatic cancer cells: a platform for drug testing

Author

Rovithi, Maria, Avan, Amir, Funel, Niccola, Leon, Leticia G., Gomez, Valentina E., Wurdinger, Thomas, Griffioen, Arjan W., Verheul, Henk M. W., and Giovannetti, Elisa

Abstract

The aim of the present study was to develop chick-embryo chorioallantoic membrane (CAM) bioluminescent tumor models employing low passage cell cultures obtained from primary pancreatic ductal adenocarcinoma (PDAC) cells. Primary PDAC cells transduced with lentivirus expressing Firefly-luciferase (Fluc) were established and inoculated onto the CAM membrane, with >80% engraftment. Fluc signal reliably correlated with tumor growth. Tumor features were evaluated by immunohistochemistry and genetic analyses, including analysis of mutations and mRNA expression of PDAC pivotal genes, as well as microRNA (miRNA) profiling. These studies showed that CAM tumors had histopathological and genetic characteristic comparable to the original tumors. We subsequently tested the modulation of key miRNAs and the activity of gemcitabine and crizotinib on CAM tumors, showing that combination treatment resulted in 63% inhibition of tumor growth as compared to control (p < 0.01). These results were associated with reduced expression of miR-21 and increased expression of miR-155. Our study provides the first evidence that transduced primary PDAC cells can form tumors on the CAM, retaining several histopathological and (epi)genetic characteristics of original tumors. Moreover, our results support the use of these models for drug testing, providing insights on molecular mechanisms underlying antitumor activity of new drugs/combinations.

Published
2017
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48. The miR-200c/141-ZEB2-TGFβ axis is aberrant in human T-cell prolymphocytic leukemia.

Author

Erkeland SJ, Stavast CJ, Schilperoord-Vermeulen J, Dal Collo G, Van de Werken HJG, Leon LG, Van Hoven-Beijen A, Van Zuijen I, Mueller YM, Bindels EM, De Ridder D, Kappers-Klunne MC, Van Lom K, Van der Velden VHJ, and Langerak AW

Subjects
Gene Expression Profiling, Humans, Lymphocytes, Transforming Growth Factor beta, Zinc Finger E-box Binding Homeobox 2 genetics, Leukemia, Prolymphocytic, T-Cell diagnosis, Leukemia, Prolymphocytic, T-Cell genetics, Leukemia, Prolymphocytic, T-Cell therapy, MicroRNAs genetics
Abstract

T-cell prolymphocytic leukemia (T-PLL) is mostly characterized by aberrant expansion of small- to medium-sized prolymphocytes with a mature post-thymic phenotype, high aggressiveness of the disease and poor prognosis. However, T-PLL is more heterogeneous with a wide range of clinical, morphological, and molecular features, which occasionally impedes the diagnosis. We hypothesized that T-PLL consists of phenotypic and/or genotypic subgroups that may explain the heterogeneity of the disease. Multi-dimensional immuno-phenotyping and gene expression profiling did not reveal clear T-PLL subgroups, and no clear T-cell receptor a or β CDR3 skewing was observed between different T-PLL cases. We revealed that the expression of microRNA (miRNA) is aberrant and often heterogeneous in T-PLL. We identified 35 miRNA that were aberrantly expressed in T-PLL with miR-200c/141 as the most differentially expressed cluster. High miR- 200c/141 and miR-181a/181b expression was significantly correlated with increased white blood cell counts and poor survival. Furthermore, we found that overexpression of miR-200c/141 correlated with downregulation of their targets ZEB2 and TGFβR3 and aberrant TGFβ1- induced phosphorylated SMAD2 (p-SMAD2) and p-SMAD3, indicating that the TGFβ pathway is affected in T-PLL. Our results thus highlight the potential role for aberrantly expressed oncogenic miRNA in T-PLL and pave the way for new therapeutic targets in this disease.

Published
2022
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49. Responsiveness of chronic lymphocytic leukemia cells to B-cell receptor stimulation is associated with low expression of regulatory molecules of the nuclear factor-κB pathway.

Author

Meijers RWJ, Muggen AF, Leon LG, de Bie M, van Dongen JJM, Hendriks RW, and Langerak AW

Subjects
Humans, I-kappa B Proteins, Receptors, Antigen, B-Cell genetics, Signal Transduction, Leukemia, Lymphocytic, Chronic, B-Cell genetics, NF-kappa B metabolism
Abstract

Chronic lymphocytic leukemia (CLL) is a disease with heterogeneous clinical and biological characteristics. Differences in Ca 2+ levels among cases, both basal and upon B-cell receptor (BCR) stimulation, may reflect heterogeneity in the pathogenesis due to cell-intrinsic factors. Our aim was to elucidate cell-intrinsic differences between BCR-responsive and -unresponsive cases. We therefore determined BCR responsiveness ex vivo based on Ca 2+ influx upon α-IgM stimulation of purified CLL cell fractions from 52 patients. Phosphorylation levels of various BCR signaling molecules, and expression of activation markers were assessed by flow cytometry. Transcription profiling of responsive (n=6) and unresponsive cases (n=6) was performed by RNA sequencing. Real-time quantitative polymerase chain reaction analysis was used to validate transcript level differences in a larger cohort. In 24 cases an α-IgM response was visible by Ca 2+ influx which was accompanied by higher phosphorylation of PLCγ2 and Akt after α-IgM stimulation in combination with higher surface expression of IgM, IgD, CD19, CD38 and CD43 compared to the unresponsive cases (n=28). Based on RNA sequencing analysis several components of the canonical nuclear factor (NF)-κB pathway, especially those related to NF-κB inhibition, were expressed more highly in unresponsive cases. Moreover, upon α-IgM stimulation, the expression of these NF-κB pathway genes (especially genes coding for NF-κB pathway inhibitors but also NF-κB subunit REL ) was upregulated in BCR-responsive cases while the level did not change, compared to basal level, in the unresponsive cases. These findings suggest that cells from CLL cases with enhanced NF-κB signaling have a lesser capacity to respond to BCR stimulation., (Copyright© 2020 Ferrata Storti Foundation.)

Published
2020
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