4th Palermo Conference on INNOVATIVE THERAPIES FOR LYMPHOID MALIGNANCIES
Published online 16 July 2009
Haematologica, Vol 94, Issue 11, 1590-1594 doi:10.3324/haematol.2009.005967
Copyright © 2009 by Ferrata Storti Foundation
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Acute Myeloid Leukemia

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

The concept of tumor immunosurveillance has raised prospects for natural killer cell-based immunotherapy of human cancer. The cure of acute myeloid leukemia may depend on eradication of leukemic stem cells, the self-renewing component of leukemia. Whether natural killer cells can recognize and lyse leukemic stem cells is not known. To develop strategies that effectively target acute myeloid leukemia-leukemic stem cells, we investigated anti-leukemic effects of human alloreactive single KIR+ natural killer cells. Natural killer effectors with KIR specificity mismatched with respect to HLA class I allotype of target cells effectively recognized acute myeloid leukemia-leukemic stem cells 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 increased the activating NKG2D ligand-dependent lysis of acute myeloid leukemia-CD34+CD38– leukemic stem cells. These results show that alloreactive natural killer cells have the potential to detect and target leukemic stem cells, and thus to improve the treatment outcome in acute myeloid leukemia.

Key words: acute leukemia, stem cells, natural killer, immunotherapy.