PortalPublikationenGP130 activation induces myeloma and collaborates with MYC

GP130 activation induces myeloma and collaborates with MYC

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GP130 activation induces myeloma and collaborates with MYC. / Dechow, Tobias; Steidle, Sabine; Götze, 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, Jürgen; Peschel, Christian; Duyster, Justus; Rose-John, Stefan; Bassermann, Florian; Keller, Ulrich.

in: J CLIN INVEST, Jahrgang 124, Nr. 12, 12.2014, S. 5263-74.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Dechow, T, Steidle, S, Götze, KS, Rudelius, M, Behnke, K, Pechloff, K, Kratzat, S, Bullinger, L, Fend, F, Soberon, V, Mitova, N, Li, Z, Thaler, M, Bauer, J, Pietschmann, E, Albers, C, Grundler, R, Schmidt-Supprian, M, Ruland, J, Peschel, C, Duyster, J, Rose-John, S, Bassermann, F & Keller, U 2014, 'GP130 activation induces myeloma and collaborates with MYC', J CLIN INVEST, Jg. 124, Nr. 12, S. 5263-74. https://doi.org/10.1172/JCI69094

APA

Dechow, T., Steidle, S., Götze, K. S., Rudelius, M., Behnke, K., Pechloff, K., Kratzat, S., Bullinger, L., Fend, F., Soberon, V., Mitova, N., Li, Z., Thaler, M., Bauer, J., Pietschmann, E., Albers, C., Grundler, R., Schmidt-Supprian, M., Ruland, J., ... Keller, U. (2014). GP130 activation induces myeloma and collaborates with MYC. J CLIN INVEST, 124(12), 5263-74. https://doi.org/10.1172/JCI69094

Vancouver

Dechow T, Steidle S, Götze KS, Rudelius M, Behnke K, Pechloff K et al. GP130 activation induces myeloma and collaborates with MYC. J CLIN INVEST. 2014 Dez;124(12):5263-74. https://doi.org/10.1172/JCI69094

Bibtex

@article{9fe583b76fbe413eb14b50a845875440,
title = "GP130 activation induces myeloma and collaborates with MYC",
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. ",
keywords = "Animals, Cell Line, Tumor, Cytokine Receptor gp130, Female, Humans, Male, Mice, Mice, Inbred BALB C, Multiple Myeloma, Neoplasms, Experimental, Plasma Cells, Proto-Oncogene Proteins c-myc, STAT3 Transcription Factor, Signal Transduction, Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't",
author = "Tobias Dechow and Sabine Steidle and G{\"o}tze, {Katharina S} and Martina Rudelius and Kerstin Behnke and Konstanze Pechloff and Susanne Kratzat and Lars Bullinger and Falko Fend and Valeria Soberon and Nadya Mitova and Zhoulei Li and Markus Thaler and Jan Bauer and Elke Pietschmann and Corinna Albers and Rebekka Grundler and Marc Schmidt-Supprian and J{\"u}rgen Ruland and Christian Peschel and Justus Duyster and Stefan Rose-John and Florian Bassermann and Ulrich Keller",
year = "2014",
month = dec,
doi = "10.1172/JCI69094",
language = "English",
volume = "124",
pages = "5263--74",
journal = "J CLIN INVEST",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "12",

}

RIS

TY - JOUR

T1 - GP130 activation induces myeloma and collaborates with MYC

AU - Dechow, Tobias

AU - Steidle, Sabine

AU - Götze, Katharina S

AU - Rudelius, Martina

AU - Behnke, Kerstin

AU - Pechloff, Konstanze

AU - Kratzat, Susanne

AU - Bullinger, Lars

AU - Fend, Falko

AU - Soberon, Valeria

AU - Mitova, Nadya

AU - Li, Zhoulei

AU - Thaler, Markus

AU - Bauer, Jan

AU - Pietschmann, Elke

AU - Albers, Corinna

AU - Grundler, Rebekka

AU - Schmidt-Supprian, Marc

AU - Ruland, Jürgen

AU - Peschel, Christian

AU - Duyster, Justus

AU - Rose-John, Stefan

AU - Bassermann, Florian

AU - Keller, Ulrich

PY - 2014/12

Y1 - 2014/12

N2 - 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.

AB - 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.

KW - Animals

KW - Cell Line, Tumor

KW - Cytokine Receptor gp130

KW - Female

KW - Humans

KW - Male

KW - Mice

KW - Mice, Inbred BALB C

KW - Multiple Myeloma

KW - Neoplasms, Experimental

KW - Plasma Cells

KW - Proto-Oncogene Proteins c-myc

KW - STAT3 Transcription Factor

KW - Signal Transduction

KW - Clinical Trial

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1172/JCI69094

DO - 10.1172/JCI69094

M3 - SCORING: Journal article

C2 - 25384216

VL - 124

SP - 5263

EP - 5274

JO - J CLIN INVEST

JF - J CLIN INVEST

SN - 0021-9738

IS - 12

ER -