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14 results on '"Pechloff, Konstanze"'

5. GP130 activation induces myeloma and collaborates with MYC

Author

Dechow, Tobias, Steidle, Sabine, Gotze, Katharina S., Rudelius, Martina, Behnke, Kerstin, Pechloff, Konstanze, Kratzat, Susanne, Bullinger, Lars, Fend, Falko, Soberon, Valeria, Mitova, Nadya, Li, Zhoulei, Thaler, Markus, Bauer, Jan, Pietschmann, Elke, Albers, Corinna, Grundler, Rebekka, Schmidt-Supprian, Marc, Ruland, Jurgen, Peschel, Christian, Duyster, Justus, Rose- John, Stefan, Bassermann, Florian, and Keller, Ulrich

Subjects
Interleukin-6 -- Physiological aspects -- Research, B cells -- Analysis -- Physiological aspects -- Research, Multiple myeloma -- Analysis -- Development and progression -- Research, Health care industry
Abstract

Multiple myeloma (MM) is a plasma cell neoplasm that results from clonal expansion of an Ig-secreting terminally differentiated B cell. Advanced MM is characterized by tissue damage that involves bone, kidney, and other organs and is typically associated with recurrent genetic abnormalities. IL-6 signaling via the IL-6 signal transducer GP130 has been implicated as an important driver of MM pathogenesis. Here, we demonstrated that ectopic expression of constitutively active GP130 (L-GP130) in a murine retroviral transduction-transplantation model induces rapid MM development of high penetrance. L-GP130-expressing mice recapitulated all of the characteristics of human disease, including monoclonal gammopathy, BM infiltration with lytic bone lesions, and protein deposition in the kidney. Moreover, the disease was easily transplantable and allowed different therapeutic options to be evaluated in vitro and in vivo. Using this model, we determined that GP130 signaling collaborated with MYC to induce MM and was responsible and sufficient for directing the plasma cell phenotype. Accordingly, we identified Myc aberrations in the L-GP130 MM model. Evaluation of human MM samples revealed recurrent activation of STAT3, a downstream target of GP130 signaling. Together, our results indicate that deregulated GP130 activity contributes to MM pathogenesis and that pathways downstream of GP130 activity have potential as therapeutic targets in MM., Introduction Multiple myeloma (MM; also referred to as plasma cell myeloma) is a B-lineage cancer characterized by the expansion of malignant plasma cells predominantly within the BM. Clinical characteristics of [...]

Published
2014
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6. Keratinocyte-intrinsic BCL10/MALT1 activity initiates and amplifies psoriasiform skin inflammation

Author

Kurgyis, Zsuzsanna, primary, Vornholz, Larsen, additional, Pechloff, Konstanze, additional, Kemény, Lajos V., additional, Wartewig, Tim, additional, Muschaweckh, Andreas, additional, Joshi, Abhinav, additional, Kranen, Katja, additional, Hartjes, Lara, additional, Möckel, Sigrid, additional, Steiger, Katja, additional, Hameister, Erik, additional, Volz, Thomas, additional, Mellett, Mark, additional, French, Lars E., additional, Biedermann, Tilo, additional, Korn, Thomas, additional, and Ruland, Jürgen, additional

Published
2021
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7. Activated gp130 signaling selectively targets B cell differentiation to induce mature lymphoma and plasmacytoma

Author

Scherger, Anna K., primary, Al-Maarri, Mona, additional, Maurer, Hans C., additional, Schick, Markus, additional, Maurer, Sabine, additional, Öllinger, Rupert, additional, Gonzalez-Menendez, Irene, additional, Martella, Manuela, additional, Thaler, Markus, additional, Pechloff, Konstanze, additional, Steiger, Katja, additional, Sander, Sandrine, additional, Ruland, Jürgen, additional, Rad, Roland, additional, Quintanilla-Martinez, Leticia, additional, Wunderlich, Frank T., additional, Rose-John, Stefan, additional, and Keller, Ulrich, additional

Published
2019
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8. Erratum: PD-1 is a haploinsufficient suppressor of T cell lymphomagenesis

Author

Wartewig, Tim, primary, Kurgyis, Zsuzsanna, additional, Keppler, Selina, additional, Pechloff, Konstanze, additional, Hameister, Erik, additional, Öllinger, Rupert, additional, Maresch, Roman, additional, Buch, Thorsten, additional, Steiger, Katja, additional, Winter, Christof, additional, Rad, Roland, additional, and Ruland, Jürgen, additional

Published
2017
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10. Constitutive gp130-JAK-STAT3 Signaling Induces a Plasma Cell Disorder Representing Genetic and Clinical Features of Human Myeloma – a Novel in Vivo Model for the Patient Subgroup Characterized By a STAT3 Target Gene Signature

Author

Steidle, Sabine, primary, Dechow, Tobias, additional, Götze, Katharina, additional, Rudelius, Martina, additional, Pechloff, Konstanze, additional, Behnke, Kerstin, additional, Bullinger, Lars, additional, Fend, Falko, additional, Valeria, Soberon, additional, Schmidt-Supprian, Marc, additional, Bassermann, Florian, additional, Ruland, Jürgen, additional, Peschel, Christian, additional, and Keller, Ulrich, additional

Published
2014
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13. The fusion kinase ITK-SYK mimics a T cell receptor signal and drives oncogenesis in conditional mouse models of peripheral T cell lymphoma

Author

Pechloff, Konstanze, primary, Holch, Julian, additional, Ferch, Uta, additional, Schweneker, Marc, additional, Brunner, Kristina, additional, Kremer, Markus, additional, Sparwasser, Tim, additional, Quintanilla-Martinez, Leticia, additional, Zimber-Strobl, Ursula, additional, Streubel, Berthold, additional, Gewies, Andreas, additional, Peschel, Christian, additional, and Ruland, Jürgen, additional

Published
2010
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14. The fusion kinase ITK-SYK mimics a T cell receptor signal and drives oncogenesis in conditional mouse models of peripheral T cell lymphoma.

Author

Pechloff K, Holch J, Ferch U, Schweneker M, Brunner K, Kremer M, Sparwasser T, Quintanilla-Martinez L, Zimber-Strobl U, Streubel B, Gewies A, Peschel C, and Ruland J

Subjects
Animals, Antigens, CD genetics, Antigens, Differentiation, T-Lymphocyte genetics, Chromosomes, Human, Pair 5 genetics, Chromosomes, Human, Pair 9 genetics, Disease Models, Animal, Embryonic Stem Cells physiology, Gene Expression Regulation, Neoplastic, Humans, Interleukin-2 genetics, Intracellular Signaling Peptides and Proteins genetics, Intracellular Signaling Peptides and Proteins metabolism, Lectins, C-Type genetics, Lymphoma, T-Cell, Peripheral pathology, Lymphoproliferative Disorders genetics, Lymphoproliferative Disorders pathology, Mice, Protein-Tyrosine Kinases genetics, Receptors, Antigen, T-Cell genetics, Receptors, Antigen, T-Cell immunology, Recombinant Fusion Proteins metabolism, Signal Transduction, Spleen enzymology, Syk Kinase, Translocation, Genetic, Lymphoma, T-Cell, Peripheral genetics, Protein-Tyrosine Kinases metabolism
Abstract

Peripheral T cell lymphomas (PTCLs) are highly aggressive malignancies with poor prognosis. Their molecular pathogenesis is not well understood and small animal models for the disease are lacking. Recently, the chromosomal translocation t(5;9)(q33;q22) generating the interleukin-2 (IL-2)-inducible T cell kinase (ITK)-spleen tyrosine kinase (SYK) fusion tyrosine kinase was identified as a recurrent event in PTCL. We show that ITK-SYK associates constitutively with lipid rafts in T cells and triggers antigen-independent phosphorylation of T cell receptor (TCR)-proximal proteins. These events lead to activation of downstream pathways and acute cellular outcomes that correspond to regular TCR ligation, including up-regulation of CD69 or production of IL-2 in vitro or deletion of thymocytes and activation of peripheral T cells in vivo. Ultimately, conditional expression of patient-derived ITK-SYK in mice induces highly malignant PTCLs with 100% penetrance that resemble the human disease. Our work demonstrates that constitutively enforced antigen receptor signaling can, in principle, act as a powerful oncogenic driver. Moreover, we establish a robust clinically relevant and genetically tractable model of human PTCL.

Published
2010
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