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25 results on '"Mangolini, Maurizio"'

1. MYC sensitises cells to apoptosis by driving energetic demand

Author

Edwards-Hicks, Joy, Su, Huizhong, Mangolini, Maurizio, Yoneten, Kubra K., Wills, Jimi, Rodriguez-Blanco, Giovanny, Young, Christine, Cho, Kevin, Barker, Heather, Muir, Morwenna, Guerrieri, Ania Naila, Li, Xue-Feng, White, Rachel, Manasterski, Piotr, Mandrou, Elena, Wills, Karen, Chen, Jingyu, Abraham, Emily, Sateri, Kianoosh, Qian, Bin-Zhi, Bankhead, Peter, Arends, Mark, Gammoh, Noor, von Kriegsheim, Alex, Patti, Gary J., Sims, Andrew H., Acosta, Juan Carlos, Brunton, Valerie, Kranc, Kamil R., Christophorou, Maria, Pearce, Erika L., Ringshausen, Ingo, and Finch, Andrew J.

Published
2022
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2. Viral transduction of primary human lymphoma B cells reveals mechanisms of NOTCH-mediated immune escape

Author

Mangolini, Maurizio, Maiques-Diaz, Alba, Charalampopoulou, Stella, Gerhard-Hartmann, Elena, Bloehdorn, Johannes, Moore, Andrew, Giachetti, Giorgia, Lu, Junyan, Roamio Franklin, Valar Nila, Chilamakuri, Chandra Sekkar Reddy, Moutsopoulos, Ilias, Rosenwald, Andreas, Stilgenbauer, Stephan, Zenz, Thorsten, Mohorianu, Irina, D’Santos, Clive, Deaglio, Silvia, Hodson, Daniel J., Martin-Subero, Jose I., and Ringshausen, Ingo

Published
2022
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3. Multi-omics reveals clinically relevant proliferative drive associated with mTOR-MYC-OXPHOS activity in chronic lymphocytic leukemia

Author

Lu, Junyan, Cannizzaro, Ester, Meier-Abt, Fabienne, Scheinost, Sebastian, Bruch, Peter-Martin, Giles, Holly A. R., Lütge, Almut, Hüllein, Jennifer, Wagner, Lena, Giacopelli, Brian, Nadeu, Ferran, Delgado, Julio, Campo, Elías, Mangolini, Maurizio, Ringshausen, Ingo, Böttcher, Martin, Mougiakakos, Dimitrios, Jacobs, Andrea, Bodenmiller, Bernd, Dietrich, Sascha, Oakes, Christopher C., Zenz, Thorsten, and Huber, Wolfgang

Published
2021
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5. Robust CRISPR-Cas9 Genetic Editing of Primary Chronic Lymphocytic Leukemia and Mantle Cell Lymphoma Cells

Author

Mateos-Jaimez, Judith, Mangolini, Maurizio, Vidal, Anna, Kulis, Marta, Colomer, Dolors, Campo, Elias, Ringshausen, Ingo, Martin-Subero, Jose I, Maiques-Diaz, Alba, Ringshausen, Ingo [0000-0002-7247-311X], and Apollo - University of Cambridge Repository

Subjects
3201 Cardiovascular Medicine and Haematology, 32 Biomedical and Clinical Sciences, 3211 Oncology and Carcinogenesis
Published
2023

7. Notch2 controls non-autonomous Wnt-signalling in chronic lymphocytic leukaemia

Author

Mangolini, Maurizio, Götte, Frederik, Moore, Andrew, Ammon, Tim, Oelsner, Madlen, Lutzny-Geier, Gloria, Klein-Hitpass, Ludger, Williamson, James C., Lehner, Paul J., Dürig, Jan, Möllmann, Michael, Rásó-Barnett, Lívia, Hughes, Katherine, Santoro, Antonella, Méndez-Ferrer, Simón, Oostendorp, Robert A. J., Zimber-Strobl, Ursula, Peschel, Christian, Hodson, Daniel J., Schmidt-Supprian, Marc, and Ringshausen, Ingo

Published
2018
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9. MYC sensitises cells to apoptosis by driving energetic demand

Author

Wellcome Trust, Cancer Research UK, Barts Charity, Medical Research Council (UK), Edwards-Hicks, Joy, Su, Huizhong, Mangolini, Maurizio, Yoneten, Kubra K., Wills, Jimi, Rodriguez-Blanco, Giovanny, Young, Christine, Cho, Kevin, Barker, Heather, Muir, Morwenna, Guerrieri, Ania Naila, Li, Xue-Feng, White, Rachel, Manasterski, Piotr, Mandrou, Elena, Wills, Karen, Chen, Jingyu, Abraham, Emily, Sateri, Kianoosh, Qian, Bin-Zhi, Bankhead, Peter, Arends, Mark, Gammoh, Noor, Kriegsheim, Alexvon, Patti, Gary J., Sim, Andrew H., Acosta, Juan C., Brunton, Valerie G., Kranc, Kamil R., Christophorou, Maria, Pearce, Erika L., Ringshausen, Ingo, Finch, Andrew J., Wellcome Trust, Cancer Research UK, Barts Charity, Medical Research Council (UK), Edwards-Hicks, Joy, Su, Huizhong, Mangolini, Maurizio, Yoneten, Kubra K., Wills, Jimi, Rodriguez-Blanco, Giovanny, Young, Christine, Cho, Kevin, Barker, Heather, Muir, Morwenna, Guerrieri, Ania Naila, Li, Xue-Feng, White, Rachel, Manasterski, Piotr, Mandrou, Elena, Wills, Karen, Chen, Jingyu, Abraham, Emily, Sateri, Kianoosh, Qian, Bin-Zhi, Bankhead, Peter, Arends, Mark, Gammoh, Noor, Kriegsheim, Alexvon, Patti, Gary J., Sim, Andrew H., Acosta, Juan C., Brunton, Valerie G., Kranc, Kamil R., Christophorou, Maria, Pearce, Erika L., Ringshausen, Ingo, and Finch, Andrew J.

Abstract

The MYC oncogene is a potent driver of growth and proliferation but also sensitises cells to apoptosis, which limits its oncogenic potential. MYC induces several biosynthetic programmes and primary cells overexpressing MYC are highly sensitive to glutamine withdrawal suggesting that MYC-induced sensitisation to apoptosis may be due to imbalance of metabolic/energetic supply and demand. Here we show that MYC elevates global transcription and translation, even in the absence of glutamine, revealing metabolic demand without corresponding supply. Glutamine withdrawal from MRC-5 fibroblasts depletes key tricarboxylic acid (TCA) cycle metabolites and, in combination with MYC activation, leads to AMP accumulation and nucleotide catabolism indicative of energetic stress. Further analyses reveal that glutamine supports viability through TCA cycle energetics rather than asparagine biosynthesis and that TCA cycle inhibition confers tumour suppression on MYC-driven lymphoma in vivo. In summary, glutamine supports the viability of MYC-overexpressing cells through an energetic rather than a biosynthetic mechanism.

Published
2022

10. NOTCH1 drives immune-escape mechanisms in B cell malignancies

Author

Mangolini, Maurizio, primary, Maiques-Diaz, Alba, additional, Charalampopoulou, Stella, additional, Gerhard-Hartmann, Elena, additional, Bloehdorn, Johannes, additional, Moore, Andrew, additional, Lu, Junyan, additional, Franklin, Valar Nila Roamio, additional, Chilamakuri, Chandra Sekkar Reddy, additional, Moutsoupoulos, Ilias, additional, Rosenwald, Andreas, additional, Stilgenbauer, Stephan, additional, Zenz, Thorsten, additional, Mohorianu, Irina, additional, D’Santos, Clive, additional, Deaglio, Silvia, additional, Martin-Subero, Jose I., additional, and Ringshausen, Ingo, additional

Published
2021
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11. Abstract PO-62: Overcoming venetoclax resistance in B-cell malignancies by antagonism of stromal TGF-beta-mediated drug resistance

Author

Park, Eugene, primary, Chen, Jingyu, additional, Moore, Andrew, additional, Mangolini, Maurizio, additional, Byod, Joseph R., additional, Schjerven, Hilde, additional, Williamson, James C., additional, Lehner, Paul J., additional, Leitges, Michael, additional, Egle, Alexander, additional, Schmidt-Supprian, Marc, additional, Frietze, Seth, additional, and Ringshausen, Ingo, additional

Published
2020
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12. ARHGEF4 Regulates an Essential Oncogenic Program in t(12;21)-Associated Acute Lymphoblastic Leukemia

Author

Virely, Clemence, primary, Gasparoli, Luca, additional, Mangolini, Maurizio, additional, Clesham, Katherine, additional, Inglott, Sarah, additional, Edwards, Darren, additional, Adams, Stuart, additional, Bartram, Jack, additional, Samarasinghe, Sujith, additional, Ancliff, Philip, additional, Vora, Ajay, additional, de Boer, Jasper, additional, and Williams, Owen, additional

Published
2020
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13. Lgr5-mediated restraint of β-catenin is essential for B-lymphopoiesis and leukemia-initiation

Author

Cosgun, Kadriye Nehir, primary, Robinson, Mark E., additional, Deb, Gauri, additional, Yang, Xin, additional, Xiao, Gang, additional, Sadras, Teresa, additional, Lee, Jaewoong, additional, Chan, Lai N., additional, Kume, Kohei, additional, Mangolini, Maurizio, additional, Winchester, Janet, additional, Chen, Zhengshan, additional, Yang, Lu, additional, Geng, Huimin, additional, Izraeli, Shai, additional, Song, Joo, additional, Chan, Wing-Chung, additional, Polson, Andrew G., additional, Jumaa, Hassan, additional, Clevers, Hans, additional, and Müschen, Markus, additional

Published
2020
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15. Stromal cell protein kinase C-β inhibition enhances chemosensitivity in B cell malignancies and overcomes drug resistance

Author

Park, Eugene, primary, Chen, Jingyu, additional, Moore, Andrew, additional, Mangolini, Maurizio, additional, Santoro, Antonella, additional, Boyd, Joseph R., additional, Schjerven, Hilde, additional, Ecker, Veronika, additional, Buchner, Maike, additional, Williamson, James C., additional, Lehner, Paul J., additional, Gasparoli, Luca, additional, Williams, Owen, additional, Bloehdorn, Johannes, additional, Stilgenbauer, Stephan, additional, Leitges, Michael, additional, Egle, Alexander, additional, Schmidt-Supprian, Marc, additional, Frietze, Seth, additional, and Ringshausen, Ingo, additional

Published
2020
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16. Lgr5 Enables Positive B-Cell Selection and Tumor-Initiation in B-Cell Malignancies

Author

Cosgun, Kadriye Nehir, primary, Deb, Gauri, additional, Yang, Xin, additional, Xiao, Gang, additional, Sadras, Teresa, additional, Auer, Franziska, additional, Lee, Jaewoong, additional, Abarientos, Anthony, additional, Mangolini, Maurizio, additional, Aghajanirefah, Ali, additional, Geng, Huimin, additional, Jumaa, Hassan, additional, Polson, Andrew G., additional, Clevers, Hans, additional, and Muschen, Markus, additional

Published
2018
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17. LGR5 Mediates Positive B-Cell Selection and is Critical for Survival of Normal and Transformed B Cells

Author

Cosgun, Kadriye Nehir, primary, Yang, Xin, additional, Mangolini, Maurizio, additional, Xiao, Gang, additional, Abarientos, Anthony, additional, Aghajanirefah, Ali, additional, Klemm, Lars, additional, Sadras, Teresa, additional, Geng, Huimin, additional, Yang, Lu, additional, Song, Qingxiao, additional, Zeng, Deye, additional, Zeng, Defu, additional, Jumaa, Hassan, additional, Polson, Andrew, additional, Clevers, Hans, additional, and Muschen, Markus, additional

Published
2018
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18. Abstract 4515: Lgr5 mediates positive B-cell selection and is critical for initiation and survival of B-cell malignancies

Author

Cosgun, Kadriye Nehir, primary, Hecht, Anna, additional, Yang, Xin, additional, Mangolini, Maurizio, additional, Aghajanirefah, Ali, additional, Xiao, Gang, additional, Sadras, Teresa, additional, Chen, Zhengshan, additional, Klemm, Lars, additional, Geng, Huimin, additional, Hong, Chao, additional, Song, Qingxiao, additional, Zeng, Deye, additional, Jumaa, Hassan, additional, Zeng, Defu, additional, Clevers, Hans, additional, and Muschen, Markus, additional

Published
2018
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23. Notch2 controls non-autonomous Wnt-signalling in chronic lymphocytic leukaemia

Author

Mangolini, Maurizio, Götte, Frederik, Moore, Andrew, Ammon, Tim, Oelsner, Madlen, Lutzny-Geier, Gloria, Klein-Hitpass, Ludger, Williamson, James C, Lehner, Paul J, Dürig, Jan, Möllmann, Michael, Rásó-Barnett, Lívia, Hughes, Katherine, Santoro, Antonella, Méndez-Ferrer, Simón, Oostendorp, Robert AJ, Zimber-Strobl, Ursula, Peschel, Christian, Hodson, Daniel J, Schmidt-Supprian, Marc, and Ringshausen, Ingo

Subjects
Bone Marrow Cells, Mesenchymal Stem Cells, Receptor Cross-Talk, Cellular Reprogramming, Leukemia, Lymphocytic, Chronic, B-Cell, 3. Good health, Cell Line, Mice, immune system diseases, hemic and lymphatic diseases, Animals, Humans, Receptor, Notch2, Wnt Signaling Pathway, beta Catenin
Abstract

The Wnt signalling pathway, one of the core de-regulated pathways in chronic lymphocytic leukaemia (CLL), is activated in only a subset of patients through somatic mutations. Here we describe alternative, microenvironment-dependent mechanisms of Wnt activation in malignant B cells. We show that tumour cells specifically induce Notch2 activity in mesenchymal stromal cells (MSCs) required for the transcription of the complement factor C1q. MSC-derived C1q in turn inhibits Gsk3-β mediated degradation of β-catenin in CLL cells. Additionally, stromal Notch2 activity regulates N-cadherin expression in CLL cells, which interacts with and further stabilises β-catenin. Together, these stroma Notch2-dependent mechanisms induce strong activation of canonical Wnt signalling in CLL cells. Pharmacological inhibition of the Wnt pathway impairs microenvironment-mediated survival of tumour cells. Similarly, inhibition of Notch signalling diminishes survival of stroma-protected CLL cells in vitro and disease engraftment in vivo. Notch2 activation in the microenvironment is a pre-requisite for the activation of canonical Wnt signalling in tumour cells.

24. The Role of SMAD7Downstream of TEL-AML1 Signalling in t(12;21) Acute Lymphoblastic Leukemia

Author

Sundaresh, Aishwarya, Mangolini, Maurizio, de Boer, Jasper, Hubank, Mike, Goulden, Nicholas, and Williams, Owen

Abstract

The single most frequent chromosomal translocation associated with childhood ALL is the t(12;21) rearrangement that creates a fusion gene between TEL (ETV6)and AML1 (RUNX1). Although TEL-AML1+patients have very good prognoses, relapses occur in up to 20% of patients and many patients face long-term side effects of chemotherapy.

Published
2015
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25. Stromal cell protein kinase C-β inhibition enhances chemosensitivity in B cell malignancies and overcomes drug resistance

Author

Paul J. Lehner, Owen Williams, Michael Leitges, Hilde Schjerven, Maike Buchner, Luca Gasparoli, Marc Schmidt-Supprian, Eugene Park, Antonella Santoro, Stephan Stilgenbauer, Maurizio Mangolini, Johannes Bloehdorn, Joseph R. Boyd, Alexander Egle, Seth Frietze, James C Williamson, Ingo Ringshausen, Andrew M. Moore, Veronika Ecker, Jingyu Chen, Park, Eugene [0000-0001-8432-5168], Chen, Jingyu [0000-0002-1941-8621], Moore, Andrew [0000-0002-2875-6315], Mangolini, Maurizio [0000-0002-0074-7935], Santoro, Antonella [0000-0002-1012-888X], Boyd, Joseph R [0000-0002-8969-9676], Schjerven, Hilde [0000-0001-9287-3375], Lehner, Paul J [0000-0001-9383-1054], Gasparoli, Luca [0000-0002-6146-2124], Bloehdorn, Johannes [0000-0003-1433-9702], Leitges, Michael [0000-0003-4203-6995], Egle, Alexander [0000-0003-0648-4416], Frietze, Seth [0000-0003-4058-3661], Ringshausen, Ingo [0000-0002-7247-311X], and Apollo - University of Cambridge Repository

Subjects
MAPK/ERK pathway, Stromal cell, Chemistry, Kinase, Apoptosis, General Medicine, Article, medicine.anatomical_structure, Drug Resistance, Neoplasm, Protein Kinase C beta, medicine, Cancer research, Tumor Cells, Cultured, Cytotoxic T cell, Humans, Signal transduction, Phosphorylation, Stromal Cells, Cytotoxicity, B cell, Protein kinase C, Signal Transduction
Abstract

Overcoming drug resistance remains a key challenge to cure patients with acute and chronic B cell malignancies. Here, we describe a stromal cell–autonomous signaling pathway, which contributes to drug resistance of malignant B cells. We show that protein kinase C (PKC)–β–dependent signals from bone marrow–derived stromal cells markedly decrease the efficacy of cytotoxic therapies. Conversely, small-molecule PKC-β inhibitors antagonize prosurvival signals from stromal cells and sensitize tumor cells to targeted and nontargeted chemotherapy, resulting in enhanced cytotoxicity and prolonged survival in vivo. Mechanistically, stromal PKC-β controls the expression of adhesion and matrix proteins, required for activation of phosphoinositide 3-kinases (PI3Ks) and the extracellular signal–regulated kinase (ERK)–mediated stabilization of B cell lymphoma–extra large (BCL-X L ) in tumor cells. Central to the stroma-mediated drug resistance is the PKC-β–dependent activation of transcription factor EB, regulating lysosome biogenesis and plasma membrane integrity. Stroma-directed therapies, enabled by direct inhibition of PKC-β, enhance the effectiveness of many antileukemic therapies.

Published
2020

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