CD99 is a therapeutic target on disease stem cells in myeloid malignancies

Stephen S. Chung, William S. Eng, Wenhuo Hu, Mona Khalaj, Francine E. Garrett-Bakelman, Montreh Tavakkoli, Ross L. Levine, Martin Carroll, Virginia M. Klimek, Ari M. Melnick, Christopher Y. Park

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36 Scopus citations

Abstract

Acute myeloid leukemia (AML) and the myelodysplastic syndromes (MDS) are initiated and sustained by selfrenewing malignant stem cells; thus, eradication of AML and MDS stem cells is required for cure. We identified CD99 as a cell surface protein frequently overexpressed on AML and MDS stem cells. Expression of CD99 allows for prospective separation of leukemic stem cells (LSCs) from functionally normal hematopoietic stem cells in AML, and high CD99 expression on AML blasts enriches for functional LSCs as demonstrated by limiting dilution xenotransplant studies. Monoclonal antibodies (mAbs) targeting CD99 induce the death of AML and MDS cells in a SARC family kinase-dependent manner in the absence of immune effector cells or complement, and anti- CD99 mAbs exhibit antileukemic activity in AML xenografts. These data establish CD99 as a marker of AML and MDS stem cells, as well as a promising therapeutic target in these disorders. 2017

Original languageEnglish (US)
Article numbereaaj2025
JournalScience Translational Medicine
Volume9
Issue number374
DOIs
StatePublished - Jan 25 2017
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)

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    Chung, S. S., Eng, W. S., Hu, W., Khalaj, M., Garrett-Bakelman, F. E., Tavakkoli, M., Levine, R. L., Carroll, M., Klimek, V. M., Melnick, A. M., & Park, C. Y. (2017). CD99 is a therapeutic target on disease stem cells in myeloid malignancies. Science Translational Medicine, 9(374), [eaaj2025]. https://doi.org/10.1126/scitranslmed.aaj2025