CD200 expression marks leukemia stem cells in human AML

Blood Advances - Tập 4 - Trang 5402-5413 - 2020
Jenny M. Ho1,2, Stephanie M. Dobson1, Veronique Voisin3, Jessica McLeod1, James A. Kennedy1,4,5, Amanda Mitchell1, Liqing Jin1, Kolja Eppert6, Gary Bader3, Mark D. Minden1,4,5,7, John E. Dick1,8, Jean C.Y. Wang1,4,5
1Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
2Department of Medicine, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada
3Terrence Donnelly Centre for Cellular and Biomedical Research, University of Toronto, Toronto, ON, Canada;
4Division of Medical Oncology and Hematology, University Health Network, Toronto, ON, Canada
5Department of Medicine, University of Toronto, Toronto, ON, Canada
6Department of Pediatrics, McGill University, Montreal, QC, Canada
7Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada
8Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada

Tóm tắt

Abstract The leukemia stem cell (LSC) populations of acute myeloid leukemia (AML) exhibit phenotypic, genetic, and functional heterogeneity that contribute to therapy failure and relapse. Progress toward understanding the mechanistic basis for therapy resistance in LSCs has been hampered by difficulties in isolating cell fractions that enrich for the entire heterogeneous population of LSCs within individual AML samples. We previously reported that CD200 gene expression is upregulated in LSC-containing AML fractions. Here, we show that CD200 is present on a greater proportion of CD45dim blasts compared with more differentiated CD45high cells in AML patient samples. In 75% (49 of 65) of AML cases we examined, CD200 was expressed on ≥10% of CD45dim blasts; of these, CD200 identified LSCs within the blast population in 9 of 10 (90%) samples tested in xenotransplantation assays. CD200+ LSCs could be isolated from CD200+ normal HSCs with the use of additional markers. Notably, CD200 expression captured both CD34– and CD34+ LSCs within individual AML samples. Analysis of highly purified CD200+ LSC-containing fractions from NPM1-mutated AMLs, which are commonly CD34–, exhibited an enrichment of primitive gene expression signatures compared with unfractionated cells. Overall, our findings support CD200 as a novel LSC marker that is able to capture the entire LSC compartment from AML patient samples, including those with NPM1 mutation.

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Blood Advances

Tập 4

5402-5413

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