Interferon-alpha-induced biologic modifications in patients with chronic myelogenous leukemia.

A M Liberati, M A Horisberger, P Garofani, V De Angelis, A Ferrajoli, F Di Clemente, P Caricchi, D Adiuto, L Fedeli, B Palumbo
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引用次数: 8

Abstract

Serum neopterin (Np), beta 2-microglobulin (beta 2-M), and 2',5'-adenylate (2',5'A) levels and intracellular 2',5'A and human Mx (Hu-Mx) protein synthesis were measured in 20-24 chronic myeloid leukemia patients before and during 1 year of IFN-alpha treatment and in a further 8-9 patients before and at the end of the first and second treatment weeks only. Univariate analysis showed that IFN-alpha increased Np and 2',5'A serum levels and intracellular concentrations of 2',5'A and Hu-Mx significantly from the end of the first week to month 12 of therapy. The biologic marker profiles were similar in cytogenetic responders and nonresponders, as well as in patients treated with IFN-alpha early (< 12 months from diagnosis) or late (after > 12 months standard chemotherapy). Further, there were no differences in the short-term (first 14 days) or long-term (during 12 month therapy) induction of the biologic markers irrespective of whether IFN-alpha 2a or IFN-alpha 2b was given. Because multivariate analysis revealed no significant interactions between cytogenetic response, time to treatment, and type of IFN-alpha used, increments in intracellular 2',5'A and Hu-Mx protein were similar at all study times for all factor combinations tested. Np levels varied significantly only during the first 14 therapy days; changes in serum 2',5'A were never statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)

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干扰素-α诱导的慢性骨髓性白血病患者的生物学改变。
在 20-24 名慢性髓性白血病患者接受 IFN-α 治疗前和治疗一年期间,以及另外 8-9 名患者接受 IFN-α 治疗前和治疗第一周和第二周结束时,测量了他们的血清蝶呤(Np)、β 2-微球蛋白(β 2-M)和 2',5'-腺苷酸(2',5'A)水平以及细胞内 2',5'A 和人类 Mx(Hu-Mx)蛋白合成情况。单变量分析显示,从治疗第一周结束到第 12 个月,IFN-α 能显著提高 Np 和 2',5'A 的血清水平以及 2',5'A 和 Hu-Mx 的细胞内浓度。细胞遗传学应答者和非应答者,以及接受 IFN-α 治疗早期(诊断后 12 个月内)或晚期(标准化疗后 12 个月内)患者的生物标志物情况相似。此外,无论使用 IFN-α 2a 还是 IFN-α 2b,在短期(最初 14 天)或长期(12 个月的治疗期间)诱导生物标志物方面均无差异。由于多变量分析显示细胞遗传学反应、治疗时间和所使用的 IFN-α 类型之间没有明显的交互作用,因此在所有研究时间内,所有测试因子组合的细胞内 2',5'A和 Hu-Mx 蛋白增量相似。Np水平仅在治疗的前14天有明显变化;血清中2',5'A的变化从未有过统计学意义。
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Interferon-alpha-induced biologic modifications in patients with chronic myelogenous leukemia. Interferon-stimulated response element and NF kappa B sites cooperate to regulate double-stranded RNA-induced transcription of the IP-10 gene. Rapid activation of the interferon-gamma signal transduction pathway by inhibitors of tyrosine phosphatases. Human indoleamine 2,3-dioxygenase inhibits Toxoplasma gondii growth in fibroblast cells. Defective transport of herpes simplex virus glycoprotein in interferon-treated cells: role of intracellular pH.
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