Do preclinical studies suggest that CD99 is a potential therapeutic target in acute myeloid leukemia and the myelodysplastic syndromes?

Acute myeloid leukemia (AML) and the myelodysplastic syndromes (MDS) are clonal hematopoietic neoplasms that arise from leukemia stem cells (LSCs) and hematopoietic stem cells (HSCs), respectively. Standard chemotherapy can efficiently eliminate the bulk of neoplastic cells, however, LSCs and MDS HSCs are relatively resistant to these therapies and can reinitiate and maintain disease. CD99 is a 32-kDa transmembrane polypeptide that is highly expressed on disease stem cells in the vast majority of AML and MDS. Areas covered: In this editorial, we focus on the current literature surrounding the identification of CD99 as a marker of MDS and AML stem cells and preclinical studies revealing the therapeutic efficacy of targeting CD99 in these diseases. Expert opinion/commentary: Cytotoxic CD99 monoclonal antibodies represent promising stem cell-directed therapies that have the potential to markedly improve clinical outcomes for these difficult-to-treat hematologic malignancies.