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目的研究STI571对慢性髓细胞白血病(CML)树突状细胞(DC)发育的影响。方法分离CML患者及正常人的骨髓单个核细胞,将实验分为CML实验组、CML对照组及正常对照组。CML对照组及正常对照组:在培养体系中加入重组人粒单核细胞集落刺激因子(rhGM-CSF)和重组人白细胞介素4(rhIL-4)培养;CML实验组:在对照组的基础上,再加入药物STI571培养。于实验第8天,各组加入重组人肿瘤坏死因子α(rhTNF-α)进一步刺激成熟。Wright染色观察细胞形态,流式细胞仪检测细胞表型,荧光原位杂交(FISH)进行细胞遗传学分析,混合淋巴细胞反应(MLR)检测抗原递呈功能;ELISA法检测培养上清中血管内皮生长因子(VEGF)的浓度。结果各组均呈现典型的树突状细胞形态;CML实验组CD80、CD86、CD83和HLA-DR的表达均显著高于CML对照组(P<0．05),经FISH证实,CML DC来源于白血病细胞;各组DC均具有刺激同种异体T淋巴细胞增殖的能力,CML实验组刺激淋巴细胞增殖的能力显著高于CML对照组(P<0．05),而与正常对照组相似(P>0．05); CML实验组VEGF的浓度较CML对照组显著降低(P<0．D5)。结论STI571可促进CML骨髓来源DC的活化,可能与其抑制了CML细胞VEGF的过度分泌,从而解除了VEGF对CML DC的分化抑制有关。
Objective To investigate the effect of STI571 on dendritic cell (DC) development in chronic myeloid leukemia (CML). Methods The bone marrow mononuclear cells of CML patients and normal individuals were separated and divided into CML experimental group, CML control group and normal control group. CML control group and normal control group: cultured rhGM-CSF and recombinant human interleukin-4 (rhIL-4) were cultured in culture system; CML experimental group: basing on control group On, then add the drug STI571 culture. On the 8th day of experiment, recombinant human tumor necrosis factor alpha (rhTNF-α) was added into each group to further stimulate maturation. Wright staining was used to observe the cell morphology, flow cytometry was used to detect the cell phenotype, FISH was used for cytogenetic analysis and mixed lymphocyte reaction (MLR) was used to detect the antigen presenting function. ELISA was used to detect the vascular endothelial The concentration of growth factor (VEGF). Results The typical dendritic cell morphology was observed in all groups. The expressions of CD80, CD86, CD83 and HLA-DR in CML group were significantly higher than those in CML control group (P <0.05) Leukemia cells; DC of all groups had the ability of stimulating the proliferation of allogeneic T lymphocytes; the ability of CML experimental group to stimulate lymphocyte proliferation was significantly higher than that of CML control group (P <0.05), but similar to that of normal control group (P > 0.05). The concentration of VEGF in CML experimental group was significantly lower than that in CML control group (P <0.D5). Conclusion STI571 can promote the activation of CML-derived DCs, which may be related to the inhibition of the excessive secretion of VEGF in CML cells.