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| Verfasst von: | Khoo, Weng Hua [VerfasserIn]  |
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| | Ledergor, Guy [VerfasserIn] |
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| | Weiner, Assaf [VerfasserIn] |
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| | Roden, Daniel L. [VerfasserIn] |
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| | Terry, Rachael L. [VerfasserIn] |
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| | McDonald, Michelle M. [VerfasserIn] |
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| | Chai, Ryan C. [VerfasserIn] |
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| | Veirman, Kim De [VerfasserIn] |
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| | Owen, Katie L. [VerfasserIn] |
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| | Opperman, Khatora S. [VerfasserIn] |
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| | Vandyke, Kate [VerfasserIn] |
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| | Clark, Justine R. [VerfasserIn] |
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| | Seckinger, Anja [VerfasserIn] |
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| | Kovacic, Natasa [VerfasserIn] |
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| | Nguyen, Akira [VerfasserIn] |
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| | Mohanty, Sindhu T. [VerfasserIn] |
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| | Pettitt, Jessica A. [VerfasserIn] |
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| | Xiao, Ya [VerfasserIn] |
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| | Corr, Alexander P. [VerfasserIn] |
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| | Seeliger, Christine [VerfasserIn] |
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| | Novotny, Mark [VerfasserIn] |
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| | Lasken, Roger S. [VerfasserIn] |
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| | Nguyen, Tuan V. [VerfasserIn] |
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| | Oyajobi, Babatunde O. [VerfasserIn] |
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| | Aftab, Dana [VerfasserIn] |
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| | Swarbrick, Alexander [VerfasserIn] |
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| | Parker, Belinda [VerfasserIn] |
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| | Hewett, Duncan R. [VerfasserIn] |
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| | Hose, Dirk [VerfasserIn] |
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| | Vanderkerken, Karin [VerfasserIn] |
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| | Zannettino, Andrew C. W. [VerfasserIn] |
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| | Amit, Ido [VerfasserIn] |
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| | Phan, Tri Giang [VerfasserIn] |
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| | Croucher, Peter I. [VerfasserIn] |
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| Titel: | A niche-dependent myeloid transcriptome signature defines dormant myeloma cells |
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| Verf.angabe: | Weng Hua Khoo, Guy Ledergor, Assaf Weiner, Daniel L. Roden, Rachael L. Terry, Michelle M. McDonald, Ryan C. Chai, Kim De Veirman, Katie L. Owen, Khatora S. Opperman, Kate Vandyke, Justine R. Clark, Anja Seckinger, Natasa Kovacic, Akira Nguyen, Sindhu T. Mohanty, Jessica A. Pettitt, Ya Xiao, Alexander P. Corr, Christine Seeliger, Mark Novotny, Roger S. Lasken, Tuan V. Nguyen, Babatunde O. Oyajobi, Dana Aftab, Alexander Swarbrick, Belinda Parker, Duncan R. Hewett, Dirk Hose, Karin Vanderkerken, Andrew C.W. Zannettino, Ido Amit, Tri Giang Phan and Peter I. Croucher |
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| E-Jahr: | 2019 |
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| Jahr: | April 25, 2019 |
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| Umfang: | 15 S. |
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| Fussnoten: | Gesehen am 25.07.2019 |
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| Titel Quelle: | Enthalten in: Blood |
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| Ort Quelle: | Washington, DC : American Society of Hematology, 1946 |
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| Jahr Quelle: | 2019 |
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| Band/Heft Quelle: | 134(2019), 1, Seite 30-43 |
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| ISSN Quelle: | 1528-0020 |
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| Abstract: | The era of targeted therapies has seen significant improvements in depth of response, progression-free survival, and overall survival for patients with multiple myeloma. Despite these improvements in clinical outcome, patients inevitably relapse and require further treatment. Drug-resistant dormant myeloma cells that reside in specific niches within the skeleton are considered a basis of disease relapse but remain elusive and difficult to study. Here, we developed a method to sequence the transcriptome of individual dormant myeloma cells from the bones of tumor-bearing mice. Our analyses show that dormant myeloma cells express a distinct transcriptome signature enriched for immune genes and, unexpectedly, genes associated with myeloid cell differentiation. These genes were switched on by coculture with osteoblastic cells. Targeting AXL, a gene highly expressed by dormant cells, using small-molecule inhibitors released cells from dormancy and promoted their proliferation. Analysis of the expression of AXL and coregulated genes in human cohorts showed that healthy human controls and patients with monoclonal gammopathy of uncertain significance expressed higher levels of the dormancy signature genes than patients with multiple myeloma. Furthermore, in patients with multiple myeloma, the expression of this myeloid transcriptome signature translated into a twofold increase in overall survival, indicating that this dormancy signature may be a marker of disease progression. Thus, engagement of myeloma cells with the osteoblastic niche induces expression of a suite of myeloid genes that predicts disease progression and that comprises potential drug targets to eradicate dormant myeloma cells. |
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| DOI: | doi:10.1182/blood.2018880930 |
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| URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
Volltext ; Verlag: http://dx.doi.org/10.1182/blood.2018880930 |
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| | Volltext: http://www.bloodjournal.org/content/134/1/30 |
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| | DOI: https://doi.org/10.1182/blood.2018880930 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| K10plus-PPN: | 167003982X |
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| Verknüpfungen: | → Zeitschrift |
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¬A¬ niche-dependent myeloid transcriptome signature defines dormant myeloma cells / Khoo, Weng Hua [VerfasserIn]; April 25, 2019 (Online-Ressource)
