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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)
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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
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
Language english
Publication Year 2016
HGF-reported in Year 2016
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.
Reviewing status Peer reviewed
Institute(s) Research Unit Gene Vector (AGV)
Institute of Computational Biology (ICB)
POF-Topic(s) 30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
30203 - Molecular Targets and Therapies
30205 - Bioengineering and Digital Health
Research field(s) Immune Response and Infection
Enabling and Novel Technologies
PSP Element(s) G-501590-001
G-501500-004
G-503800-001
G-553800-001
DOI 10.1016/j.ccell.2016.11.002
WOS ID WOS:000389967400008
Scopus ID 85004073453
Erfassungsdatum 2016-12-31
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