CD93 is expressed on chronic myeloid leukemia stem cells and identifies a quiescent population which persists after tyrosine kinase inhibitor therapy



Kinstrie, Ross, Horne, Gillian A, Morrison, Heather, Irvine, David, Munje, Chinmay, Castaneda, Eduardo Gomez, Moka, Hothri A, Dunn, Karen, Cassels, Jennifer E, Parry, Narissa
et al (show 6 more authors) (2020) CD93 is expressed on chronic myeloid leukemia stem cells and identifies a quiescent population which persists after tyrosine kinase inhibitor therapy. LEUKEMIA, 34 (6). pp. 1613-1625.

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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<sup>-</sup>CD34<sup>+</sup>CD38<sup>-</sup>CD90<sup>+</sup> 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<sup>-</sup> 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<sup>-</sup>CD34<sup>+</sup>CD38<sup>-</sup>CD90<sup>+</sup> CML LSC population with stem cell characteristics and may be an important indicator in determining poor TKI responders.

Item Type: Article
Uncontrolled Keywords: Animals, Humans, Mice, Neoplasm, Residual, Membrane Glycoproteins, Receptors, Complement, Protein Kinase Inhibitors, Drug Resistance, Neoplasm, Neoplastic Stem Cells, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Heterografts, Biomarkers, Tumor
Depositing User: Symplectic Admin
Date Deposited: 19 Feb 2020 13:49
Last Modified: 19 Jan 2023 00:02
DOI: 10.1038/s41375-019-0684-5
Open Access URL: https://www.nature.com/articles/s41375-019-0684-5
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URI: https://livrepository.liverpool.ac.uk/id/eprint/3075730