Remission maintenance in acute myeloid leukemia: impact of functional histamine H2 receptors expressed by leukemic cells
Remission maintenance in acute myeloid leukemia: impact of functional histamine H2 receptors expressed by leukemic cells
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DOI：
10.3324/haematol.2012.066399
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发表时间：
2012-12-01
期刊：
影响因子：
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通讯作者：
Thoren, Fredrik B.
中科院分区：
文献类型：
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作者：
Aurelius, Johan;Martner, Anna;Thoren, Fredrik B.
在III期临床试验中，使用二盐酸组胺和白细胞介素-2的巩固后免疫治疗已被证明可改善急性髓性白血病的无白血病生存期。在这项研究中，在145例急性髓性白血病患者中确定了治疗效果，这些患者的形态学形式由法国-美国-英国分类定义。M4/M5（粒单核细胞/单核细胞）白血病患者的无白血病生存率显著提高，但M2（成髓细胞）白血病患者的无白血病生存率无显著提高。我们还分析了组胺H-2受体表达的白血病细胞恢复从26个新诊断的患者。H-2受体通常不存在于M2细胞中，但经常由M4/M5细胞表达。M4/M5细胞，而不是M2细胞，产生活性氧，引发相邻的自然杀伤细胞的凋亡。这些事件被二盐酸组胺显著抑制。我们的数据表明，存在功能性组胺H2受体对人类AML细胞，并表明这些受体的表达白血病细胞可能会影响组胺为基础的免疫治疗的有效性。
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 H-2 receptor expression by leukemic cells recovered from 26 newly diagnosed patients. H-2 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.