Remission maintenance in acute myeloid leukemia: impact of functional histamine H2 receptors expressed by leukemic cells
Johan Aurelius,
Anna Martner,
Mats Brune,
Lars Palmqvist,
Markus Hansson,
Kristoffer Hellstrand,
Fredrik B. Thoren
Affiliations
Johan Aurelius
Department of Sahlgrenska Cancer Center, University of Gothenburg, Sweden;Infectious Diseases, The Sahlgrenska Academy, University of Gothenburg, Sweden
Anna Martner
Department of Sahlgrenska Cancer Center, University of Gothenburg, Sweden;Infectious Diseases, The Sahlgrenska Academy, University of Gothenburg, Sweden
Mats Brune
Hematology, The Sahlgrenska Academy, University of Gothenburg, Sweden
Lars Palmqvist
Clinical Chemistry and Transfusion Medicine, The Sahlgrenska Academy, University of Gothenburg, Sweden
Markus Hansson
Department of Hematology, Skåne University Hospital, Sweden
Kristoffer Hellstrand
Department of Sahlgrenska Cancer Center, University of Gothenburg, Sweden;Infectious Diseases, The Sahlgrenska Academy, University of Gothenburg, Sweden
Fredrik B. Thoren
Department of Sahlgrenska Cancer Center, University of Gothenburg, Sweden;Infectious Diseases, The Sahlgrenska Academy, University of Gothenburg, Sweden
Post-consolidation immunotherapy with histamine dihydrochloride and interleukin-2 has been shown to improve leukemia-free survival in acute myeloid leukemia in a phase III trial. For this study, treatment efficacy was determined among 145 trial patients with morphological forms of acute myeloid leukemia as defined by the French-American-British classification. Leukemia-free survival was strongly improved in M4/M5 (myelomonocytic/monocytic) leukemia but not in M2 (myeloblastic) leukemia. We also analyzed histamine H2 receptor expression by leukemic cells recovered from 26 newly diagnosed patients. H2 receptors were typically absent from M2 cells but frequently expressed by M4/M5 cells. M4/M5 cells, but not M2 cells, produced reactive oxygen species that triggered apoptosis in adjacent natural killer cells. These events were significantly inhibited by histamine dihydrochloride. Our data demonstrate the presence of functional histamine H2 receptors on human AML cells and suggest that expression of these receptors by leukemic cells may impact on the effectiveness of histamine-based immunotherapy.
