TitleCD99 is a therapeutic target on disease stem cells in myeloid malignancies.
Publication TypeJournal Article
Year of Publication2017
AuthorsChung, Stephen S., Eng William S., Hu Wenhuo, Khalaj Mona, Garrett-Bakelman Francine E., Tavakkoli Montreh, Levine Ross L., Carroll Martin, Klimek Virginia M., Melnick Ari M., and Park Christopher Y.
JournalSci Transl Med
Date Published2017 Jan 25
Keywords12E7 Antigen, Animals, Antibodies, Monoclonal, Apoptosis, Cell Membrane, Cell Separation, Female, Flow Cytometry, Genotype, Hematopoietic Stem Cells, Humans, Leukemia, Myeloid, Acute, Male, Mice, Myelodysplastic Syndromes, Neoplasm Transplantation, Research Design, Treatment Outcome

<p>Acute myeloid leukemia (AML) and the myelodysplastic syndromes (MDS) are initiated and sustained by self-renewing 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.</p>

Alternate JournalSci Transl Med
PubMed ID28123069
PubMed Central IDPMC5624309
Grant ListK08 CA169055 / CA / NCI NIH HHS / United States
K08 CA194275 / CA / NCI NIH HHS / United States
P30 CA008748 / CA / NCI NIH HHS / United States