Anti-thymocyte globulin’s activity against acute myeloid leukemia stem cells View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2019-04

AUTHORS

Rosy Dabas, Poonam Dharmani-Khan, Monica Modi, Tiffany Van Slyke, Joanne Luider, Don Morris, Joseph Brandwein, Andrew Daly, Faisal M. Khan, Jan Storek

ABSTRACT

Rabbit anti-thymocyte globulin (ATG (Thymoglobulin)) kills T cells in vitro and probably also in vivo as it prevents graft-vs-host disease (GvHD) in patients. Recently we demonstrated that ATG at a clinically relevant concentration (10-50 mg/L) kills in vitro not only T cells but also leukemic blasts. In the present study, we investigated whether ATG kills not only leukemic blasts but also leukemic stem cells (LSCs). We used a flow cytometric assay of complement-mediated cytotoxicity (CDC). ATG-induced death of acute myeloid leukemia (AML) cells from patients newly diagnosed with AML was measured among blasts as well as LSCs. At 10 mg/L ATG, blasts but not LSCs were killed. At 50 mg/L ATG, both blasts and LSCs were killed. We also measured ATG-mediated killing of healthy individuals' hematopoietic stem cells (HSCs). Median 2% HSCs from blood and 15% HSCs from filgrastim-mobilized grafts were killed with 50 mg/L ATG, compared to 30% LSCs from the blood of AML patients (p = 0.001 and 0.022, respectively). In conclusion, LSCs are sensitive to ATG, however, only at a relatively high ATG concentration. At that concentration, LSCs are killed to a higher degree than HSCs. More... »

PAGES

1-11

References to SciGraph publications

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41409-018-0296-0

    DOI

    http://dx.doi.org/10.1038/s41409-018-0296-0

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1106149898

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/30108326


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