BMSEHA15
Published online 16 July 2009
(Haematologica 2009, 10.3324/haematol.2009.005967)
Copyright © 2009 by Ferrata Storti Foundation
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Brief Reports

Human acute myeloid leukemia CD34+CD38– stem cells are susceptible to allorecognition and lysis by single KIR-expressing natural killer cells

Ulrich Langenkamp1, Uwe Siegler1,2, Simon Jörger1, Stefan Diermayr1, Alois Gratwohl2, Christian P. Kalberer1, 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:aleksandra.wodnar-filipowicz{at}unibas.ch

ABSTRACT

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.