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Characterization of Rare, Dormant, and Therapy-Resistant Cells in Acute Lymphoblastic Leukemia

Ebinger, S; Oezdemir, EZ; Ziegenhain, C; Tiedt, S; Alves, CC; Grunert, M; Dworzak, M; ... Jeremias, I; + view all (2016) Characterization of Rare, Dormant, and Therapy-Resistant Cells in Acute Lymphoblastic Leukemia. Cancer Cell , 30 (6) pp. 849-862. 10.1016/j.ccell.2016.11.002. Green open access

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Abstract

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.

Type: Article
Title: Characterization of Rare, Dormant, and Therapy-Resistant Cells in Acute Lymphoblastic Leukemia
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.ccell.2016.11.002
Publisher version: http://dx.doi.org/10.1016/j.ccell.2016.11.002
Language: English
Additional information: Copyright © 2016 The Author(s). Published by Elsevier Inc. This is an open access article made available under the Creative Commons Attribution 4.0 International (CC BY 4.0) license (http://creativecommons.org/licenses/by/4.0/).
Keywords: acute lymphoblastic leukemia; patient-derived xenograft (PDX) cells; dormant tumor cells; Cancer stem cells; treatment resistance; RNA single-cell sequencing; minimal residual disease (MRD); primary patients' ALL MRD cells
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Cancer Bio
URI: https://discovery.ucl.ac.uk/id/eprint/1536399
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