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首页> 外文期刊>Biomarker Research >Phosphatidylinositol 3-kinase-δ (PI3K-δ) is a potential therapeutic target in adult T-cell leukemia-lymphoma
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Phosphatidylinositol 3-kinase-δ (PI3K-δ) is a potential therapeutic target in adult T-cell leukemia-lymphoma

机译：磷脂酰肌醇3-激酶-δ（PI3K-δ）是成人T细胞白血病-淋巴瘤的潜在治疗靶标

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The prognosis of adult T-cell leukemia-lymphoma (ATL) remains very poor, and there is an urgent clinical need to investigate novel therapies for ATL. The expression of phosphatidylinositol 3-kinase-δ (PI3k-δ) is normally restricted to hematopoietic cells and is known as a key determinant of cell survival in certain cancers. The inhibitor of PI3k-δ, idelalisib, has been shown to be effective in the treatment of chronic lymphocytic leukemia. Here, we report the expression of PI3k-δ and the ability of idelalisib to promote apoptosis in ex vivo ATL samples. The activity of PI3K was quantified by a PI3-Kinase Activity ELISA kit. Although there was no significant difference in mean PI3K activity between healthy donors and patients with ATL, certain cases of ATL showed extremely high PI3K activities. The expression of PI3k-δ protein was detectable in most ATL cases. The freshly isolated cells from ATL patients were cultured with or without idelalisib for 0–10?days, and cell survival was then quantified. Idelalisib induced apoptosis in ATL cells in a time-dependent manner, and significantly reduced the frequency of viable ATL cells at 10?days. No time-dependent effects of idelalisib were observed in non-malignant T cells from the same patients. CCL22 has been reported to promote survival of ATL cells in part through the PI3K-AKT pathway. Idelalisib blocked this CCL22-induced phosphorylation of AKT and significantly inhibited the proliferation of ATL cells. These results validate the PI3K-AKT pathway as a potential therapeutic target in ATL.
机译：成人T细胞白血病-淋巴瘤（ATL）的预后仍然很差，并且迫切需要临床研究ATL的新疗法。磷脂酰肌醇3-激酶-δ（PI3k-δ）的表达通常限于造血细胞，并且已知其是某些癌症中细胞存活的关键决定因素。已经证明PI3k-δ的抑制剂艾达拉西布可有效治疗慢性淋巴细胞性白血病。在这里，我们报告PI3k-δ的表达和艾德拉西布促进离体ATL样品中细胞凋亡的能力。通过PI3-激酶活性ELISA试剂盒定量PI3K的活性。尽管健康捐献者和ATL患者的平均PI3K活性没有显着差异，但某些ATL病例显示PI3K活性极高。在大多数ATL病例中可检测到PI3k-δ蛋白的表达。从ATL患者中分离出的新鲜细胞在有或没有艾德拉西布的情况下培养0-10天，然后对细胞存活率进行定量。依达拉西布以时间依赖性方式诱导ATL细胞凋亡，并在10天时显着降低了存活ATL细胞的频率。在同一患者的非恶性T细胞中未观察到艾达拉西布的时间依赖性。据报道，CCL22部分通过PI3K-AKT途径促进ATL细胞的存活。依达拉西布阻断了CCL22诱导的AKT磷酸化，并显着抑制了ATL细胞的增殖。这些结果验证了PI3K-AKT途径是ATL中潜在的治疗靶点。

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