Kinstrie, R;
Horne, GA;
Morrison, H;
Irvine, D;
Munje, C;
Castaneda, EG;
Moka, HA;
... Copland, M; + view all
(2020)
CD93 is expressed on chronic myeloid leukemia stem cells and identifies a quiescent population which persists after tyrosine kinase inhibitor therapy.
Leukemia
10.1038/s41375-019-0684-5.
(In press).
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Abstract
The introduction of BCR-ABL tyrosine kinase inhibitors has revolutionized the treatment of chronic myeloid leukemia (CML). A major clinical aim remains the identification and elimination of low-level disease persistence, termed “minimal residual disease”. The phenomenon of disease persistence suggests that despite targeted therapeutic approaches, BCR-ABL-independent mechanisms exist which sustain the survival of leukemic stem cells (LSCs). Although other markers of a primitive CML LSC population have been identified in the preclinical setting, only CD26 appears to offer clinical utility. Here we demonstrate consistent and selective expression of CD93 on a lin {−}^CD34^{+}CD38^{−}CD90^{+} CML LSC population and show in vitro and in vivo data to suggest increased stem cell characteristics, as well as robust engraftment in patient-derived xenograft models in comparison with a CD93− CML stem/progenitor cell population, which fails to engraft. Through bulk and single-cell analyses of selected stem cell and cell survival-specific genes, we confirmed the quiescent character and demonstrate their persistence in a population of CML patient samples who demonstrate molecular relapse on TKI withdrawal. Taken together, our results identify that CD93 is consistently and selectively expressed on a lin {−}^CD34^{+}CD38^{−}CD90^{+} CML LSC population with stem cell characteristics and may be an important indicator in determining poor TKI responders.
Type: | Article |
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Title: | CD93 is expressed on chronic myeloid leukemia stem cells and identifies a quiescent population which persists after tyrosine kinase inhibitor therapy |
Open access status: | An open access version is available from UCL Discovery |
DOI: | 10.1038/s41375-019-0684-5 |
Publisher version: | https://doi.org/10.1038/s41375-019-0684-5 |
Language: | English |
Additional information: | © 2020 Springer Nature Limited. This article is licensed under a Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/). |
Keywords: | Cancer stem cells, Chronic myeloid leukaemia |
UCL classification: | UCL 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 Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept |
URI: | https://discovery.ucl.ac.uk/id/eprint/10093464 |
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