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Published online before print June 14, 2004
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,2,2
* Institute for Transfusion Medicine and Immunehaematology, Campus Virchow-Klinikum, Charité–Universitätsmedizin Berlin, Germany;
Memorial Sloan-Kettering Cancer Center, Sloan-Kettering Institute, New York, New York;
Robert-Koch-Institut, Berlin, Germany; and
Department of Pediatric Oncology, Charité, Campus Virchow-Klinikum, Humboldt-University Berlin, Germany
1 Correspondence: Institute for Transfusion Medicine and Immunhaemotology, Campus Virchow-Klinikum, Charité–Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany. E-mail: anja.moldenhauer{at}charite.de
Recurrent cytogenetic abnormalities in leukemic blasts make these an attractive source for dendritic cells (DC) to induce a leukemia-specific immune response. In this study, three leukemic cell lines were investigated: Kasumi-1 and SKNO-1 (two acute myeloid leukemia (AML) cell lines carrying the (8;21)-chromosomal translocation, resulting in the expression of the leukemia-specific fusion protein AML1-eight-twenty-one) and REH, an acute lymphoblastic leukemia cell line with the (12;21)-chromosomal translocation and expression of translocation ETS-like leukemia-AML1. These fusion proteins are implicated in the pathogenesis of the leukemic state by recruiting corepressors and histone deacetylases (HDAC), which interfere with normal cell differentiation. In vitro generation of DC was achieved using a cytokine cocktail containing tumor necrosis factor 
, granulocyte macrophage-colony stimulating factor, c-kit ligand, and soluble CD40 ligand; yet, addition of the HDAC inhibitor (Hdi) trichostatin A enhanced DC differentiation with retention of the fusion transcripts. These leukemic DC showed high-level CD83 and human leukocyte antigen (HLA)-DR expression and had a high allostimulatory potential. Only DC generated from these cell lines after Hdi induced blast-specific cytotoxic T cell responses in HLA-A-matched T cells with a cytotoxicity of 42% in parental Kasumi-1 and 83% in parental REH cells, respectively. This model system suggests that the Hdi supports the in vitro differentiation of DC from leukemic blasts with AML1-containing fusion proteins.
Key Words: leukemia • translocation • vaccination
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