Saturday, July 18, 2009

Alloreactive NK cells detect and target leukemic SCs

Human acute myeloid leukemia CD34+CD38– stem cells are susceptible to allorecognition and lysis by single KIR-expressing natural killer cells by Ulrich Langenkamp and 6 co-authors, including Aleksandra Wodnar-Filipowicz, Haematologica 2009(Jul 16) [Epub ahead of print][FriendFeed entry][Early version of the full text PDF]. PubMed 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.

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