吲哚胺2,3-二氧化酶在人急性单核细胞白血病(M_5)和急性淋巴细胞白血病细胞中的表达及其抑制剂1-甲基色氨酸的治疗作用(英文)

Indoleamine 2,3-Dioxygenase Expression in Cells of Human Acute Monocyte Leukemia(M_5)and Acute Lymphocyte Leukemia and Therapeutic Effect of Its Inhibitor 1-Methyl Tryptophan

本研究旨在探讨吲哚胺2,3-二氧化酶(IDO)在白血病细胞中的表达和作用。应用间接免疫荧光染色光法检测人急性单核细胞白血病(M5)和急性淋巴细胞白血病(ALL)的细胞内吲哚胺2,3-二氧化酶的表达情况,并以小鼠急性淋巴细胞白血病细胞系L1210建立白血病小鼠模型以观察吲哚胺2,3-二氧化酶抑制剂1-甲基色氨酸是否具有抑制白血病细胞生长的作用。结果表明:M5和ALL的白血病细胞中吲哚胺2,3-二氧化酶阳性细胞率分别为29.4±11.2%和24.7±7.96%,而对照组的外周血单个核细胞中吲哚胺2,3-二氧化酶阳性细胞率仅为3±1.2%;两个白血病组与正常对照组在吲哚胺2,3-二氧化酶阳性细胞率方面的差异均有显著的统计学意义(P<0.05),而M5与ALL组之间在吲哚胺2,3-二氧化酶阳性细胞率方面无显著性差异(P>0.05);1-甲基色氨酸(1-MT)治疗的白血病小鼠与对照组比较,肿瘤消退,生存期延长(P<0.05),部分治疗小鼠达到无病长期生存(注射肿瘤细胞后生存期超过3个月)。结论:人急性单核细胞白血病(M5)和急性淋巴细胞白血病(ALL)的细胞均表达吲哚胺2,3-二氧化酶,1-甲基色氨酸对白血病小鼠有一定的治疗作用。

The objective of this study was to investigate the expression and function of indoleamine 2, 3-dioxygenase （IDO） in leukemia. The IDO expressions in human acute monocyte leukemia （ M5 ） and acute lymphocyte leukemia （ALL） were detected by immunofluorescence staining. Constructed leukemia mouse model was used to observe whether the IDO inhibitor, 1-methyl tryptophan （1-MT）, has any effect in treating leukemia. The experimental group were fed with 1-MT solution every day while the mice in control group had no further treatment. The results showed that the average ratios of IDO expresson were 29.4 ± 11.2% in M5 patients and 24.7 ± 7.96% in ALL patients respectively. After statistical test, IDO expression level in leukemia cells was significantly higher than that of normal mononuclear cells. The tumor decreased gradually in mice treated with 1-MT. At the terminal point of the experiment （88 days after vaccination）, the average survival time in the experimental group was 42.3 days while the mice in control group only lived 15.1 days in average, which difference was statistically significant （ P 〈 0.05 ）. Some of the leukemia mice in the experimental group long-term survived without tumor （ more than three months after vaccination）. It is conlcuded that human acute monocyte leukemia （M5） and acute lymphocyte leukemia （ALL） express IDO, and both can be treated by 1-MT in mice.