- Ulrich Langenkamp1,
- Uwe Siegler1,2,
- Simon Jörger1,
- Stefan Diermayr1,
- Alois Gratwohl2,
- Christian P. Kalberer1 and
- Aleksandra Wodnar-Filipowicz1⇓
- 1 Experimental Hematology, Department of Biomedicine, University Hospital Basel, Basel
- 2 Division of Hematology, University Hospital Basel, Basel, Switzerland
- Correspondence: Aleksandra Wodnar-Filipowicz, Department of Biomedicine, University Hospital Basel, Hebelstrasse 20, CH-4031 Basel, Switzerland. Email:
The concept of tumor immunosurveillance has raised prospects for natural killer (NK) cell-based immunotherapy of human cancer. The cure of acute myeloid leukemia (AML) may depend on eradication of leukemic stem cells (LSCs), the self-renewing component of leukemia. Whether NK cells can recognize and lyse LSCs is not known. To develop strategies that effectively target AML-LSCs, we investigated anti-leukemic effects of human alloreactive single KIR+ NK cells. NK effectors with KIR specificity mismatched with respect to HLA class I allotype of target cells effectively recognized AML-LSCs defined phenotypically as CD34+CD38−, while healthy bone marrow-derived CD34+CD38− hematopoietic stem cells were spared, as demonstrated by cytotoxicity and hematopoietic colony-forming assays. The HDAC inhibitor valproic acid augmented the activating NKG2D ligand-dependent lysis of AML-CD34+CD38− LSCs. These results show that alloreactive NK cells have the potential to detect and target LSCs, and thus to improve the treatment outcome in AML.
- Received January 14, 2009.
- Revision received May 19, 2009.
- Accepted June 3, 2009.
- Copyright© Ferrata Storti Foundation