CD99 is a therapeutic target on disease stem cells in myeloid malignancies
| Autor: | Ari Melnick, Ross L. Levine, Mona Khalaj, Stephen S. Chung, Montreh Tavakkoli, Martin Carroll, Wenhuo Hu, Christopher Y. Park, Virginia M. Klimek, William S. Eng, Francine E. Garrett-Bakelman |
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| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine Myeloid Genotype medicine.drug_class CD99 Apoptosis Cell Separation 12E7 Antigen Biology Monoclonal antibody Article Mice 03 medical and health sciences Cancer stem cell hemic and lymphatic diseases medicine Animals Humans neoplasms Myelodysplastic syndromes Cell Membrane Antibodies Monoclonal Myeloid leukemia General Medicine Flow Cytometry Hematopoietic Stem Cells medicine.disease Leukemia Myeloid Acute Haematopoiesis Treatment Outcome 030104 developmental biology medicine.anatomical_structure Research Design Myelodysplastic Syndromes Immunology Cancer research Female Stem cell Neoplasm Transplantation |
| Zdroj: | Science Translational Medicine. 9 |
| ISSN: | 1946-6242 1946-6234 |
| Popis: | 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 (HSCs) 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 SRC-family kinase dependent manner in the absence of immune effector cells or complement, and administration of anti-CD99 mAbs exhibit anti-leukemic activity in AML xenografts. These data establish CD99 as a novel marker of AML and MDS stem cells, as well as a promising therapeutic target in these disorders. |
| Databáze: | OpenAIRE |
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