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Characterization of rare, dormant, and therapy-resistant cells in acute lymphoblastic leukemia

Tumor relapse is associated with dismal prognosis, but responsible biological principles remain incompletely understood. To isolate and characterize relapse-inducing cells, we used genetic engineering and proliferation-sensitive dyes in patient-derived xenografts of acute lymphoblastic leukemia (ALL...

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Hauptverfasser: Ebinger, Sarah (VerfasserIn) , Özdemir, Erbey Ziya (VerfasserIn) , Ziegenhain, Christoph (VerfasserIn) , Tiedt, Sebastian (VerfasserIn) , Castro Alves, Catarina (VerfasserIn) , Grunert, Michaela (VerfasserIn) , Dworzak, Michael (VerfasserIn) , Lutz, Christoph (VerfasserIn) , Turati, Virginia A. (VerfasserIn) , Enver, Tariq (VerfasserIn) , Horny, Hans-Peter (VerfasserIn) , Sotlar, Karl (VerfasserIn) , Parekh, Swati (VerfasserIn) , Spiekermann, Karsten (VerfasserIn) , Hiddemann, Wolfgang (VerfasserIn) , Schepers, Aloys (VerfasserIn) , Polzer, Bernhard (VerfasserIn) , Kirsch, Stefan (VerfasserIn) , Hoffmann, Martin (VerfasserIn) , Knapp, Bettina (VerfasserIn) , Hasenauer, Jan (VerfasserIn) , Pfeifer, Heike (VerfasserIn) , Panzer-Grümayer, Renate (VerfasserIn) , Enard, Wolfgang (VerfasserIn) , Gires, Olivier (VerfasserIn) , Jeremias, Irmela (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: December 1, 2016
In: Cancer cell
Year: 2016, Jahrgang: 30, Heft: 6, Pages: 849-862
ISSN:1878-3686
DOI:10.1016/j.ccell.2016.11.002
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.ccell.2016.11.002
Verlag, lizenzpflichtig, Volltext: http://www.sciencedirect.com/science/article/pii/S1535610816305086
Volltext
Verfasserangaben:Sarah Ebinger, Erbey Ziya Özdemir, Christoph Ziegenhain, Sebastian Tiedt, Catarina Castro Alves, Michaela Grunert, Michael Dworzak, Christoph Lutz, Virginia A. Turati, Tariq Enver, Hans-Peter Horny, Karl Sotlar, Swati Parekh, Karsten Spiekermann, Wolfgang Hiddemann, Aloys Schepers, Bernhard Polzer, Stefan Kirsch, Martin Hoffmann, Bettina Knapp, Jan Hasenauer, Heike Pfeifer, Renate Panzer-Grümayer, Wolfgang Enard, Olivier Gires, and Irmela Jeremias
Beschreibung
Zusammenfassung:Tumor relapse is associated with dismal prognosis, but responsible biological principles remain incompletely understood. To isolate and characterize relapse-inducing cells, we used genetic engineering and proliferation-sensitive dyes in patient-derived xenografts of acute lymphoblastic leukemia (ALL). We identified a rare subpopulation that resembled relapse-inducing cells with combined properties of long-term dormancy, treatment resistance, and stemness. Single-cell and bulk expression profiling revealed their similarity to primary ALL cells isolated from pediatric and adult patients at minimal residual disease (MRD). Therapeutically adverse characteristics were reversible, as resistant, dormant cells became sensitive to treatment and started proliferating when dissociated from the in vivo environment. Our data suggest that ALL patients might profit from therapeutic strategies that release MRD cells from the niche.
Beschreibung:Gesehen am 30.04.2020
Beschreibung:Online Resource
ISSN:1878-3686
DOI:10.1016/j.ccell.2016.11.002

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