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白细胞介素2治疗骨髓增生异常综合征的潜力评估。

Assessment of therapeutic potential of interleukin 2 for myelodysplastic syndromes.

作者信息

Ogata K, Yokose N, Ito T, An E, Tamura H, Dan K, Hamaguchi H, Sakamaki H, Onozawa Y, Nomura T

机构信息

Third Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.

出版信息

Br J Haematol. 1994 Mar;86(3):562-7. doi: 10.1111/j.1365-2141.1994.tb04787.x.

DOI:10.1111/j.1365-2141.1994.tb04787.x
PMID:8043438
Abstract

The therapeutic potential of interleukin 2 (IL-2) for myelodsplastic syndromes (MDS) was evaluated in vitro. IL-2-induced lymphokine-activated killer (LAK) cells were prepared from 38 MDS patients and 20 normal subjects. The cytotoxicity of LAK cells against K562 and Raji cell lines and MDS blasts was significantly reduced in high-risk MDS (refractory anaemia with excess blasts (RAEB), RAEB in transformation, and leukaemic transformation of MDS), but was relatively well-preserved in low-risk MDS (refractory anaemia (RA) and RA with ringed sideroblasts). Examination of the immunophenotypes of freshly-isolated lymphocytes showed that the percentage of CD4+ cells in low-risk MDS and the percentage of CD3+, CD4+ and CD8+ cell populations in high-risk MDS was significantly reduced compared with these populations in normal subjects. After cultivation with IL-2, these three cell populations were still reduced in the corresponding MDS groups and the percentage of CD3-CD56+ cells were significantly reduced in high-risk MDS. There was a positive correlation between the percentage of K562 cells lysed by MDS LAK cells and the percentage of CD3-CD56+ lymphocytes in MDS LAK cells. These aberrant lymphocyte subpopulations appeared to explain, at least in part, the reduced LAK cell cytotoxicity in MDS. These results present a possibility that IL-2 and LAK therapies are ineffective for most high-risk MDS patients, whereas they have potential value for low-risk MDS patients whose lymphocyte cytotoxicity is usually preserved.

摘要

白细胞介素2(IL-2)对骨髓增生异常综合征(MDS)的治疗潜力在体外进行了评估。从38例MDS患者和20名正常受试者中制备了IL-2诱导的淋巴因子激活的杀伤(LAK)细胞。高危MDS(难治性贫血伴原始细胞增多(RAEB)、RAEB转化型和MDS白血病转化型)中LAK细胞对K562和Raji细胞系以及MDS原始细胞的细胞毒性显著降低,但在低危MDS(难治性贫血(RA)和伴有环形铁粒幼细胞的RA)中相对保存较好。对新鲜分离淋巴细胞免疫表型的检测显示,与正常受试者相比,低危MDS中CD4+细胞百分比以及高危MDS中CD3+、CD4+和CD8+细胞群体百分比显著降低。用IL-2培养后,相应MDS组中这三个细胞群体仍然减少,高危MDS中CD3-CD56+细胞百分比显著降低。MDS LAK细胞裂解的K562细胞百分比与MDS LAK细胞中CD3-CD56+淋巴细胞百分比之间存在正相关。这些异常淋巴细胞亚群似乎至少部分解释了MDS中LAK细胞细胞毒性降低的原因。这些结果表明,IL-2和LAK疗法对大多数高危MDS患者无效,而对淋巴细胞细胞毒性通常保留的低危MDS患者具有潜在价值。

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Assessment of therapeutic potential of interleukin 2 for myelodysplastic syndromes.白细胞介素2治疗骨髓增生异常综合征的潜力评估。
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引用本文的文献

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Interferon-gamma and tumor necrosis factor-alpha induce an immunoinhibitory molecule, B7-H1, via nuclear factor-kappaB activation in blasts in myelodysplastic syndromes.干扰素-γ和肿瘤坏死因子-α通过核因子-κB 激活在骨髓增生异常综合征的原始细胞中诱导免疫抑制分子 B7-H1。
Blood. 2010 Aug 19;116(7):1124-31. doi: 10.1182/blood-2009-12-255125. Epub 2010 May 14.