Biological effects of bexarotene in cutaneous T-cell lymphoma
Biological effects of bexarotene in cutaneous T-cell lymphoma
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DOI：
10.1001/archderm.141.3.315
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发表时间：
2005-03-01
影响因子：
--
通讯作者：
Rook, AH
中科院分区：
文献类型：
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作者：
Budgin, JB;Richardson, SK;Rook, AH
目的：确定贝沙罗汀对从皮肤T细胞淋巴瘤白血病型患者外周血中分离的恶性T细胞的作用设计、设置和参与者：9例Sezary综合征患者外周血单个核细胞和高循环恶性T细胞负荷在一所大学的医学中心，对100名（>50%的外周血单核细胞）和6名健康志愿者进行了评估，以测试贝沙罗汀对T细胞的影响。贝沙罗汀诱导细胞凋亡的能力及其对Sezary综合征患者外周血淋巴细胞T细胞细胞因子产生的影响。结果：贝沙罗汀产生剂量依赖性的Sezary综合征患者外周血T细胞凋亡。大约三分之二的患者的T细胞始终对贝沙罗汀敏感，而其余三分之一的患者的T细胞始终对贝沙罗汀的凋亡作用具有抗性。贝沙罗汀抑制Sezary综合征患者外周血细胞产生丝裂原诱导的白细胞介素4，这种作用与患者细胞对凋亡的敏感性有关。相反，维甲酸受体特异性类维生素A，全反式维甲酸，贝沙罗汀不诱导增强干扰素γ production.Conclusions：贝沙罗汀诱导恶性T细胞的细胞凋亡与塞扎里综合征患者，但从一部分患者的细胞是耐凋亡的影响。白细胞介素4的产生，可以发挥作用，在全身免疫抑制的特点，推进塞扎里综合征，可抑制贝沙罗汀。
Objective: To determine the effects of bexarotene on malignant T cells isolated from the peripheral blood of patients with the leukemic variant of cutaneous T-cell lymphoma (Sezary syndrome).Design, Setting, and Participants: Peripheral blood mononuclear cells from 9 patients with Sezary syndrome and a high burden of circulating malignant T cells (>50% of peripheral blood mononuclear cells) and 6 healthy volunteers underwent evaluation at a university medical center, to test the effects of bexarotene on T cells.Main Outcome Measures: The capacity of bexarotene to induce apoptosis and its effects on T-cell cytokine production from peripheral blood lymphocytes isolated from patients with Sezary syndrome.Results: Bexarotene produced dose-dependent apoptosis of peripheral blood T cells from patients with Sezary syndrome. The T cells from approximately two thirds of patients were consistently sensitive to bexarotene, whereas those from the remaining one third of patients were consistently resistant to the apoptotic effects of bexarotene. Bexarotene inhibited mitogen-induced interleukin 4 production by the peripheral blood cells of patients with Sezary syndrome, and this effect correlated with sensitivity of patients' cells to apoptosis. In contrast to the retinoic acid receptor-specific retinoid, all-trans retinoic acid, bexarotene does not induce the augmentation of interferon gamma production.Conclusions: Bexarotene induces apoptosis of malignant T cells from patients with Sezary syndrome, but the cells from a proportion of patients are resistant to the apoptotic effects. Interleukin 4 production, which can play a role in the systemic immunosuppression that characterizes advancing Sezary syndrome, may be inhibited by bexarotene.