Re Francesca, Arpinati Mario, Testoni Nicoletta, Ricci Paolo, Terragna Carolina, Preda Paola, Ruggeri Deborah, Senese Barbara, Chirumbolo Gabriella, Martelli Valeria, Urbini Benedetta, Baccarani Michele, Tura Sante, Rondelli Damiano
Institute of Hematology and Medical Oncology Seràgnoli, University of Bologna, Bologna, Italy.
Exp Hematol. 2002 Feb;30(2):126-34. doi: 10.1016/s0301-472x(01)00768-8.
The aim of this study was to determine whether expression of the CD86 costimulatory molecule in acute myeloid leukemia (AML) can identify blast cells committed to the monocytic/dendritic lineage.
One hundred ten consecutive AML patients observed at diagnosis were studied by flow cytometry. In selected experiments, in vitro cultures with CD34(+)CD86(+) or CD34(-)CD86(+) blasts were performed in the presence of granulocyte-macrophage colony-stimulating actor (GM-CSF) with or without tumor necrosis factor-alpha (TNF-alpha) or GM-CSF + interleukin-4 (IL-4), respectively, to induce a dendritic differentiation, documented by morphologic and immunophenotypic assays. T-cell alloreactivity to CD86(+) AML cells and leukemic dendritic cells (AML-DC) was tested in mixed leukocyte cultures and anti-leukemic cytotoxic assays.
CD86 was expressed in 54% AML, whereas CD80 and CD1a were only occasionally positive. CD86(+) AML samples included M5 and M4, but also 47% M0-M1 FAB types, and were more frequently CD14(+) (p < 0.00001) and CD34(-) (p = 0.00005) than CD86(-)AML. Six different patterns of CD86(+) AML were identified, according to CD34 or CD14 total or partial coexpression. Four samples enriched in CD34(+)CD86(+) AML cells differentiated into AML-DC CD86(+), CD80(+), CD40(+), CD11c(+), HLA-DR(++), CD14(+/-) that also were CD1a(+) or CD83(+), after 6 days of in vitro culture with GM-CSF +/- TNF-alpha. CD34(-)CD86(+) AML cells differentiated into AML-DC after 3 to 5 days (n = 5 experiments), and trisomy 8 was found in two AML and AML-DC samples by fluorescence in situ hybridization analysis. Finally, AML-DC induced more potent allo-T-cell proliferation, cytokine release, and anti-leukemic cytotoxicity than CD86(+) blasts.
In AML, CD86 is a marker of monocytic/dendritic lineage. Because CD86(+) blasts may differentiate into DC rapidly, CD86(+)AML patients could be optimal candidates for immunotherapy studies, both in autologous and allogeneic settings.
本研究旨在确定急性髓系白血病（AML）中CD86共刺激分子的表达是否能识别向单核细胞/树突状细胞谱系分化的原始细胞。
对诊断时观察的110例连续AML患者进行流式细胞术研究。在选定的实验中，分别在存在或不存在肿瘤坏死因子-α（TNF-α）或粒细胞-巨噬细胞集落刺激因子（GM-CSF）+白细胞介素-4（IL-4）的情况下，对CD34(+)CD86(+)或CD34(-)CD86(+)原始细胞进行体外培养，以诱导树突状分化，并通过形态学和免疫表型分析进行记录。在混合白细胞培养和抗白血病细胞毒性试验中测试T细胞对CD86(+)AML细胞和白血病树突状细胞（AML-DC）的同种异体反应性。
54%的AML表达CD86，而CD80和CD1a仅偶尔呈阳性。CD86(+)AML样本包括M5和M4，但也有47%的M0-M1 FAB类型，并且比CD86(-)AML更频繁地表达CD14(+)（p < 0.00001）和CD34(-)（p = 0.00005）。根据CD34或CD14的全部或部分共表达情况，确定了六种不同模式的CD86(+)AML。四个富含CD34(+)CD86(+)AML细胞的样本在与GM-CSF +/- TNF-α进行6天体外培养后分化为CD86(+)、CD80(+)、CD40(+)、CD11c(+)、HLA-DR(++)、CD14(+/-)的AML-DC，这些AML-DC也为CD1a(+)或CD83(+)。CD34(-)CD86(+)AML细胞在3至5天后分化为AML-DC（n = 5个实验），并且通过荧光原位杂交分析在两个AML和AML-DC样本中发现了8号染色体三体。最后，AML-DC比CD86(+)原始细胞诱导更有效的同种异体T细胞增殖、细胞因子释放和抗白血病细胞毒性。
在AML中，CD86是单核细胞/树突状细胞谱系的标志物。由于CD86(+)原始细胞可能迅速分化为DC，CD86(+)AML患者可能是自体和异体环境下免疫治疗研究的最佳候选者。
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