Can immunotherapy specifically target acute myeloid leukemic stem cells?

Accumulating evidence supports the role of leukemic stem cells (LSCs) in the high relapse rate of acute myeloid leukemia (AML) patients. The clinical relevance of LSCs, which were originally characterized in xenograft models, has recently been confirmed by the finding that stem cell-like gene expression signatures can predict the clinical outcome of AML patients. The targeted elimination of LSCs might hence constitute an efficient therapeutic approach to AML. Here, we review immunotherapeutic strategies that target LSC-associated antigens, including T cell-mediated and monoclonal antibody-based regimens. Attention is given to the issue of antigen specificity because this is relevant to the therapeutic window and determines the superiority of LSC-targeting immunotherapy.