CD99 is a therapeutic target on disease stem cells in myeloid malignancies Academic Article uri icon

Overview

MeSH Major

  • Epigenesis, Genetic
  • Gene Expression Regulation, Leukemic
  • Genetic Heterogeneity
  • Leukemia, Myeloid, Acute

abstract

  • 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.

publication date

  • January 25, 2017

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC5624309

Digital Object Identifier (DOI)

  • 10.1126/scitranslmed.aaj2025

PubMed ID

  • 28123069

Additional Document Info

volume

  • 9

number

  • 374