Immunological effects of interferon-alpha on chronic myelogenous leukemia
Immunological effects of interferon-alpha on chronic myelogenous leukemia
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DOI：
10.1080/1042819031000110973
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发表时间：
2003-12-01
影响因子：
2.6
通讯作者：
Voltarelli, JC
中科院分区：
文献类型：
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作者：
de Castro, FA;Palma, PVB;Voltarelli, JC
干扰素- α治疗慢性粒细胞白血病慢性期（CML-CP）是有效的，但该物质抗白血病作用的免疫学机制尚不清楚。本研究的目的是探讨干扰素- α对慢性粒细胞白血病患者的免疫作用。采用流式细胞术检测26例CML-CP患者外周血单个核细胞（PBMC）在ifn - α治疗前和治疗后3、6、9个月的细胞活化和凋亡标志物、自然杀伤细胞（NK）细胞毒性和细胞内细胞因子（ifn - γ、IL-2和IL-4）的产生。结果与血液学反应相关。在整个患者组中，使用inf - α后，产生IL-2和ifn - γ的淋巴细胞显著增加，NK活性增加，CD34 +细胞数量减少。在26例CML患者中，经过9个月的ifn - α治疗后，15例达到血液学缓解，7例达到部分细胞遗传学缓解。CD8/FasL +、DR/CD3 +、DQ/CD3 +、CD34/Fas +、DR/CD56 +、CD56/FasL +细胞和产生ifn - γ和il -2淋巴细胞的百分比增加，NK细胞毒性仅在血液学完全缓解的患者组中增加。我们的研究结果表明，在CML-CP中使用ifn - α可减少CD34 +细胞的数量，激活T细胞，增强干细胞凋亡标志物，并增加淋巴细胞胞内ifn - γ和IL-2的产生。综上所述，这些结果表明ifn - α对CML-CP的治疗作用至少部分是由免疫机制介导的。
Treatment with interferon-alpha is effective for chronic myelogenous leukemia in the chronic phase (CML-CP), but the immunological mechanisms of the antileukemic effect of this substance are still unclear. The objective of this study was to investigate the immunological effects of interferon-alpha in CML patients. Markers of cellular activation and apoptosis, natural killer (NK) cell cytotoxicity and production of intracellular cytokines (IFN-gamma, IL-2 and IL-4) were determined by flow cytometry in the peripheral blood mononuclear cells (PBMC) of 26 CML-CP patients before and 3, 6 and 9 months after IFN-alpha treatment. The results were correlated with the hematological response. In the whole group of patients, INF-alpha use was followed by a significant increase of lymphocytes producing IL-2 and IFN-gamma, an increase in NK activity and a decrease in the number of CD34 + cells. Out of 26 CML patients, 15 achieved hematological remission and 7 achieved partial cytogenetic remission after 9 months of IFN-alpha treatment. There was an increase in the percentage of CD8/FasL + , DR/CD3 + , DQ/CD3 + , CD34/Fas + , DR/CD56 + , CD56/FasL + cells and of IFN-gamma- and IL-2-producing lymphocytes and an increase in NK cytotoxicity only in the group of patients who achieved complete hematological remission. Our results indicate that IFN-alpha use in CML-CP reduces the number of CD34 + cells, activates T cells, enhances stem cell apoptotic markers and increases the production of intracellular IFN-gamma and IL-2 by lymphocytes. Taken together, these results indicate that the therapeutic effect of IFN-alpha in CML-CP is mediated at least in part by immunological mechanisms.