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Ebinger, S. ; Özdemir, E.Z. ; Ziegenhain, C.* ; Tiedt, S. ; Castro Alves, C. ; Grunert, M. ; Dworzak, M.* ; Lutz, C.* ; Turati, V.A.* ; Enver, T.* ; Horny, H.-P.* ; Sotlar, K.* ; Parekh, S.* ; Spiekermann, K.* ; Hiddemann, W.* ; Schepers, A. ; Polzer, B.* ; Kirsch, S.* ; Hoffmann, M.* ; Knapp, B. ; Hasenauer, J. ; Pfeifer, H.* ; Panzer-Grümayer, R.* ; Enard, W.* ; Gires, O.* ; Jeremias, I.

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

Cancer Cell 30, 849-862 (2016)
Publ. Version/Full Text Research data DOI
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Acute Lymphoblastic Leukemia ; Cancer Stem Cells ; Dormant Tumor Cells ; Minimal Residual Disease (mrd) ; Patient-derived Xenograft (pdx) Cells ; Primary Patients' All Mrd Cells ; Rna Single-cell Sequencing ; Treatment Resistance; Minimal Residual Disease; Hematopoietic Stem-cells; Initiating Cells; Propagating Cells; Myeloid-leukemia; Drug Discovery; B-precursor; Cancer; Gene; Xenografts
ISSN (print) / ISBN 1535-6108
e-ISSN 1878-3686
Journal Cancer Cell
Quellenangaben Volume: 30, Issue: 6, Pages: 849-862 Article Number: , Supplement: ,
Publisher Cell Press
Publishing Place Cambridge, Mass.
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Research Unit Gene Vector (AGV)
Institute of Computational Biology (ICB)