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12 results on '"Petersen, David Leander"'

2. Expression and function of Kv1.3 channel in malignant T cells in Sézary syndrome

Author

Hu, Tengpeng, Buus, Terkild Brink, Krejsgaard, Thorbjørn, Nansen, Anneline, Lundholt, Betina Kerstin, Spee, Pieter, Fredholm, Simon, Petersen, David Leander, Blümel, Edda, Gluud, Maria, Monteiro, Madalena N, Willerslev-Olsen, Andreas, Andersen, Mads Hald, Straten, Per Thor, Met, Özcan, Stolearenco, Veronica, Fogh, Hanne, Gniadecki, Robert, Nastasi, Claudia, Litman, Thomas, Woetmann, Anders, Gjerdrum, Lise Mette Rahbek, Ødum, Niels, Hu, Tengpeng, Buus, Terkild Brink, Krejsgaard, Thorbjørn, Nansen, Anneline, Lundholt, Betina Kerstin, Spee, Pieter, Fredholm, Simon, Petersen, David Leander, Blümel, Edda, Gluud, Maria, Monteiro, Madalena N, Willerslev-Olsen, Andreas, Andersen, Mads Hald, Straten, Per Thor, Met, Özcan, Stolearenco, Veronica, Fogh, Hanne, Gniadecki, Robert, Nastasi, Claudia, Litman, Thomas, Woetmann, Anders, Gjerdrum, Lise Mette Rahbek, and Ødum, Niels

Abstract

The voltage-gated potassium channel Kv1.3 (KCNA3) is expressed by a subset of chronically activated memory T cells and plays an important role in their activation and proliferation. Here, we show that primary malignant T cells isolated from patients with Sézary syndrome (SS) express Kv1.3 and are sensitive to potent Kv1.3 inhibitors ShK and Vm24, but not sensitive to a less potent inhibitor [N17A/F32T]-AnTx. Kv1.3 blockade inhibits CD3/CD28-induced proliferation and IL-9 expression by SS cells in a concentration-dependent manner. In parallel, CD3/CD28-mediated CD25 induction is inhibited, whereas Kv1.3 blockade has no effect on apoptosis or cell death as judged by Annexin V and PI staining. In conclusion, we provide the first evidence that malignant T cells in SS express functional Kv1.3 channels and that Kv1.3 blockade inhibits activation-induced proliferation as well as cytokine and cytokine receptor expression in malignant T cells, suggesting that Kv1.3 is a potential target for therapy in SS.

Published
2019

3. Expression and function of Kv1.3 channel in malignant T cells in Sézary syndrome

Author

Hu, Tengpeng, primary, Buus, Terkild Brink, additional, Krejsgaard, Thorbjørn, additional, Nansen, Anneline, additional, Lundholt, Betina Kerstin, additional, Spee, Pieter, additional, Fredholm, Simon, additional, Petersen, David Leander, additional, Blümel, Edda, additional, Gluud, Maria, additional, Monteiro, Madalena N., additional, Willerslev-Olsen, Andreas, additional, Andersen, Mads Hald, additional, Straten, Per thor, additional, Met, Özcan, additional, Stolearenco, Veronica, additional, Fogh, Hanne, additional, Gniadecki, Robert, additional, Nastasi, Claudia, additional, Litman, Thomas, additional, Woetmann, Anders, additional, Gjerdrum, Lise Mette Rahbek, additional, and Ødum, Niels, additional

Published
2019
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4. SATB1 in malignant T cells

Author

Fredholm, Simon Mayland, Willerslev-Olsen, Andreas, Met, Özcan, Kubat, Linda, Gluud, Maria, Mathiasen, Sarah L., Friese, Christina, Blümel, Edda, Petersen, David Leander, Hu, Tengpeng, Nastasi, Claudia, Lindahl, Lise M., Buus, Terkild Brink, Krejsgaard, Thorbjørn Frej, Wasik, Mariusz A., Kopp, Katharina Luise Maria, Koralov, Sergei B., Persson, Jenny L., Bonefeld, Charlotte Menne, Geisler, Carsten, Andersen, Anders Woetmann, Iversen, Lars, Becker, Jürgen C., Ødum, Niels, Fredholm, Simon Mayland, Willerslev-Olsen, Andreas, Met, Özcan, Kubat, Linda, Gluud, Maria, Mathiasen, Sarah L., Friese, Christina, Blümel, Edda, Petersen, David Leander, Hu, Tengpeng, Nastasi, Claudia, Lindahl, Lise M., Buus, Terkild Brink, Krejsgaard, Thorbjørn Frej, Wasik, Mariusz A., Kopp, Katharina Luise Maria, Koralov, Sergei B., Persson, Jenny L., Bonefeld, Charlotte Menne, Geisler, Carsten, Andersen, Anders Woetmann, Iversen, Lars, Becker, Jürgen C., and Ødum, Niels

Abstract

Deficient expression of Suppressor Special AT-rich Binding-1 (SATB1) hampers thymocyte development and results in inept T cell lineages. Recent data implicate dysregulated SATB1 expression in the pathogenesis of mycosis fungoides (MF), the most frequent variant of cutaneous T cell lymphoma (CTCL). Here we report on a disease-stage-associated decrease of SATB1 expression and an inverse expression of STAT5 and SATB1 in situ. Importantly, STAT5 inhibited SATB1 expression through induction of miR-155. Decreased SATB1 expression triggered enhanced expression of IL-5 and IL-9 (but not IL-6 and IL-32) whereas increased SATB1 expression had the opposite effect indicating that the mir-155 target SATB1 is a repressor of IL-5 and IL-9 in malignant T cells. In accordance, inhibition of STAT5, and its upstream activator Janus Kinase-3 (Jak3), triggered increased SATB1 expression and a concomitant suppression of IL-5 and IL-9 expression in malignant T cells. In conclusion, we provide a mechanistic link between the proto-oncogenic Jak3/STAT5/miR-155 pathway, SATB1, and cytokines linked to CTCL severity and progression indicating that SATB1 dysregulation is involved in CTCL pathogenesis.

Published
2018

5. A novel BLK-induced tumor model

Author

Petersen, David Leander, Berthelsen, Jens, Willerslev-Olsen, Andreas, Fredholm, Simon, Dabelsteen, Sally, Bonefeld, Charlotte Menné, Geisler, Carsten, Woetmann, Anders, Petersen, David Leander, Berthelsen, Jens, Willerslev-Olsen, Andreas, Fredholm, Simon, Dabelsteen, Sally, Bonefeld, Charlotte Menné, Geisler, Carsten, and Woetmann, Anders

Abstract

B-lymphoid tyrosine kinase (BLK) is a non-receptor tyrosine kinase belonging to the SRC family kinases. BLK is known to be functionally involved in B-cell receptor signaling and B-cell development. New evidence suggests that B-lymphoid tyrosine kinase is ectopically expressed and is a putative oncogene in cutaneous T-cell lymphoma and other T-cell malignancies. However, little is known about the role of BLK in lymphomagenesis, and the oncogenic function seems to depend on the cellular context. Importantly, BLK is also ectopically expressed in other hematological and multiple non-hematological malignancies including breast, kidney, and lung cancers, suggesting that BLK could be a new potential target for therapy. Here, we studied the oncogenic potential of human BLK. We found that engrafted Ba/F3 cells stably expressing constitutive active human BLK formed tumors in mice, whereas neither Ba/F3 cells expressing wild type BLK nor non-transfected Ba/F3 cells did. Inhibition of BLK with the clinical grade and broadly reacting SRC family kinase inhibitor dasatinib inhibited growth of BLK-induced tumors. In conclusion, our study provides evidence that human BLK is a true proto-oncogene capable of inducing tumors, and we demonstrate a novel BLK activity-dependent tumor model suitable for studies of BLK-driven lymphomagenesis and screening of novel BLK inhibitors in vivo.

Published
2017

6. A novel BLK-induced tumor model

Author

Petersen, David Leander, primary, Berthelsen, Jens, additional, Willerslev-Olsen, Andreas, additional, Fredholm, Simon, additional, Dabelsteen, Sally, additional, Bonefeld, Charlotte Menné, additional, Geisler, Carsten, additional, and Woetmann, Anders, additional

Published
2017
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7. The Expression of IL-21 Is Promoted by MEKK4 in Malignant T Cells and Associated with Increased Progression Risk in Cutaneous T-Cell Lymphoma

Author

Fredholm, Simon, Litvinov, Ivan V, Mongan, Nigel P, Schiele, Sarah, Willerslev-Olsen, Andreas, Petersen, David Leander, Krejsgaard, Thorbjørn, Sibbesen, Nina, Nastasi, Claudia, Bonefeld, Charlotte M, Persson, Jenny L., Straten, Per Thor, Andersen, Mads Hald, Koralov, Sergei B, Wasik, Mariusz M, Geisler, Carsten, Sasseville, Denis, Woetmann, Anders, Ødum, Niels, Fredholm, Simon, Litvinov, Ivan V, Mongan, Nigel P, Schiele, Sarah, Willerslev-Olsen, Andreas, Petersen, David Leander, Krejsgaard, Thorbjørn, Sibbesen, Nina, Nastasi, Claudia, Bonefeld, Charlotte M, Persson, Jenny L., Straten, Per Thor, Andersen, Mads Hald, Koralov, Sergei B, Wasik, Mariusz M, Geisler, Carsten, Sasseville, Denis, Woetmann, Anders, and Ødum, Niels

Published
2016
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8. The Expression of IL-21 Is Promoted by MEKK4 in Malignant T Cells and Associated with Increased Progression Risk in Cutaneous T-Cell Lymphoma

Author

Fredholm, Simon, primary, Litvinov, Ivan V., additional, Mongan, Nigel P., additional, Schiele, Sarah, additional, Willerslev-Olsen, Andreas, additional, Petersen, David Leander, additional, Krejsgaard, Thorbjørn, additional, Sibbesen, Nina, additional, Nastasi, Claudia, additional, Bonefeld, Charlotte M., additional, Persson, Jenny L., additional, Straten, Per Thor, additional, Andersen, Mads Hald, additional, Koralov, Sergei B., additional, Wasik, Mariusz M., additional, Geisler, Carsten, additional, Sasseville, Denis, additional, Woetmann, Anders, additional, and Ødum, Niels, additional

Published
2016
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10. The expression of IL-21 is promoted by MEKK4 in malignant T cells and associated with increased progression risk in cutaneous T-cell lymphoma

Author

Fredholm, Simon, Livinov, Ivan, Mongan, Nigel P., Schiele, Sarah, Willerslev-Olsen, Andreas, Petersen, David Leander, Krejsgaard, Thorbjørn, Sibbesen, Nina, Nastasi, Claudia, Bonefeld, Charlotte M., Persson, Jenny L., Thor Straten, Per, Andersen, Mads Hald, Koralov, Sergei B., Wasik, Mariusz, Geisler, Carsten, Sasseville, Denis, Woetmann, Anders, Ødum, Niels, Fredholm, Simon, Livinov, Ivan, Mongan, Nigel P., Schiele, Sarah, Willerslev-Olsen, Andreas, Petersen, David Leander, Krejsgaard, Thorbjørn, Sibbesen, Nina, Nastasi, Claudia, Bonefeld, Charlotte M., Persson, Jenny L., Thor Straten, Per, Andersen, Mads Hald, Koralov, Sergei B., Wasik, Mariusz, Geisler, Carsten, Sasseville, Denis, Woetmann, Anders, and Ødum, Niels

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11. The expression of IL-21 is promoted by MEKK4 in malignant T cells and associated with increased progression risk in cutaneous T-cell lymphoma

Author

Fredholm, Simon, Livinov, Ivan, Mongan, Nigel P., Schiele, Sarah, Willerslev-Olsen, Andreas, Petersen, David Leander, Krejsgaard, Thorbjørn, Sibbesen, Nina, Nastasi, Claudia, Bonefeld, Charlotte M., Persson, Jenny L., Thor Straten, Per, Andersen, Mads Hald, Koralov, Sergei B., Wasik, Mariusz, Geisler, Carsten, Sasseville, Denis, Woetmann, Anders, Ødum, Niels, Fredholm, Simon, Livinov, Ivan, Mongan, Nigel P., Schiele, Sarah, Willerslev-Olsen, Andreas, Petersen, David Leander, Krejsgaard, Thorbjørn, Sibbesen, Nina, Nastasi, Claudia, Bonefeld, Charlotte M., Persson, Jenny L., Thor Straten, Per, Andersen, Mads Hald, Koralov, Sergei B., Wasik, Mariusz, Geisler, Carsten, Sasseville, Denis, Woetmann, Anders, and Ødum, Niels

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12. The expression of IL-21 is promoted by MEKK4 in malignant T cells and associated with increased progression risk in cutaneous T-cell lymphoma

Author

Fredholm, Simon, Livinov, Ivan, Mongan, Nigel P., Schiele, Sarah, Willerslev-Olsen, Andreas, Petersen, David Leander, Krejsgaard, Thorbjørn, Sibbesen, Nina, Nastasi, Claudia, Bonefeld, Charlotte M., Persson, Jenny L., Thor Straten, Per, Andersen, Mads Hald, Koralov, Sergei B., Wasik, Mariusz, Geisler, Carsten, Sasseville, Denis, Woetmann, Anders, Ødum, Niels, Fredholm, Simon, Livinov, Ivan, Mongan, Nigel P., Schiele, Sarah, Willerslev-Olsen, Andreas, Petersen, David Leander, Krejsgaard, Thorbjørn, Sibbesen, Nina, Nastasi, Claudia, Bonefeld, Charlotte M., Persson, Jenny L., Thor Straten, Per, Andersen, Mads Hald, Koralov, Sergei B., Wasik, Mariusz, Geisler, Carsten, Sasseville, Denis, Woetmann, Anders, and Ødum, Niels

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