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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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4. 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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5. 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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6. 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. 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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8. 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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9. 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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10. 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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11. 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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12. 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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13. 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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14. 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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15. 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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16. 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. Risk Prediction of Metachronous Colorectal Cancer from Molecular Features of Adenomas:A Nested Case-Control Study

Author

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

Abstract

Current morphologic features defining advanced adenomas (size ≥10 mm, high-grade dysplasia or ≥25% villous component) cannot optimally distinguish individuals at high risk or low risk of metachronous colorectal cancer (me-CRC), which may result in suboptimal surveillance. Certain DNA copy-number alterations (CNAs) are associated with adenoma-tocarcinoma progression. We aimed to evaluate whether these molecular features can better predict an individual's risk of me-CRC than the morphologic advanced adenoma features. In this nested case-control study, 529 individuals with a single adenoma at first colonoscopy were selected from a Norwegian adenoma cohort. DNA copy-number profileswere determined, by low-coveragewhole-genome sequencing. Prevalence of CNAs in advanced and non-advanced adenomas and its association (OR) with me-CRC was assessed. For the latter, cases (withme-CRC) were matched to controls (withoutme-CRC) on follow-up, age and sex. CNAs associated with adenoma-to-carcinoma progression were observed in 85/267 (32%) of advanced adenomas and in 27/262 (10%) of nonadvanced adenomas.me-CRC was statistically significantly associated, also after adjustment for other variables, with age at baseline [OR, 1.14; 95% confidence interval CI), 1.03-1.26; P = 0.012], advanced adenomas (OR, 2.46; 95% CI, 1.50-4.01; P < 0.001) and with the presence of ≥3 DNA copy-number losses (OR, 1.90; 95% CI. 1.02-3.54; P = 0.043). Molecularly-defined high-risk adenomas were associated with me-CRC, but the association of advanced adenoma with me-CRC was stronger.

Published
2023

18. 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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19. 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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20. 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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21. 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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22. 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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24. 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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30. 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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33. 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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35. 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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38. 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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40. 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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41. 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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43. 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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45. 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
2022
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46. 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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48. 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, M.M., Leon, Leticia G., Zeeuw, Sander A.J. van der, Mei, Hailiang, Hoen, P.A.C. 't, Roon-Mom, W.M. van, Toonen, Lodewijk J.A., Overzier, Maurice, Evers, M.M., Leon, Leticia G., Zeeuw, Sander A.J. van der, Mei, Hailiang, Hoen, P.A.C. 't, and Roon-Mom, W.M. van

Abstract

Contains fulltext : 193059.pdf (publisher's version ) (Open Access)

Published
2018

49. Molecular simplification in bioactive molecules: Formal synthesis of (+)-muconin

Author

Crisostomo, Fernando R. Pinacho, Carrillo, Romen, Leon, Leticia G., Martin, Tomas, Padron, Jose M., and Martin, Victor S.

Subjects
Polyketides -- Chemical properties, Polyketides -- Structure, Stereochemistry -- Analysis, Enantiomers -- Chemical properties, Enantiomers -- Structure, Biological sciences, Chemistry
Abstract

The concept of molecular simplification as a drug design strategy to shorten synthetic routes, while keeping or enhancing the biological activity of the lead drug, is applied to (+)-muconin, an acetogenin with remarkable cytotoxicity. A novel method that enables the stereoselective synthesis of such a natural compound or its enantiomer from a common precursor, affording complete stereochemical control and decrease in the number of chemical steps required, is described.

Published
2006

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