Common gamma chain-signaling cytokines promote proliferation of T-cell acute lymphoblastic leukemia.
Common gamma chain-signaling cytokines promote proliferation of T-cell acute lymphoblastic leukemia.
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发表时间：
2004
期刊：
影响因子：
10.1
通讯作者：
J. Barata;T. D. Keenan;A. Silva;L. Nadler;V. Boussiotis;A. Cardoso
中科院分区：
文献类型：
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作者：
J. Barata;T. D. Keenan;A. Silva;L. Nadler;V. Boussiotis;A. Cardoso
对T细胞急性淋巴细胞白血病（T-ALL）病理生理学关键信号的识别应有助于开发新的、更有效的治疗策略。常见的γ链信号细胞因子（γ-细胞因子）-白细胞介素2、4、7、9和15 -差异调节T细胞发育、存活、增殖和分化。虽然存在一些个别的细胞因子的研究，没有全面的分析Zc-细胞因子家族对恶性T细胞的影响已经报道。在这里，我们研究了Zc-细胞因子对T-ALL增殖的影响。设计与方法从诊断为T-ALL的儿童血液或骨髓中收集原代白血病细胞。根据成熟阶段对细胞进行免疫表型分析和分类。通过3 H-胸苷掺入来评估对γ-细胞因子的增殖反应。结果所有γ细胞因子均能促进原代T-ALL细胞的增殖。白细胞介素（IL）-7是最常诱导白血病细胞增殖并促进最稳健应答的细胞因子。IL-4优先刺激具有更成熟免疫表型的样本的增殖，而CD 1a阳性皮质T-ALL细胞对IL-9的反应较低。最后，两种Zc-细胞因子的组合显示出协同或相加的增殖作用。解释和结论本研究表明，所有的γ-细胞因子测试可以刺激白血病T细胞的增殖，并表明，协同效应可能发生在体内。我们首次证明IL-9和IL-15可以向T-ALL细胞提供增殖信号。重要的是，我们的研究结果支持的假设，IL-7可能作为一个关键的调节T-ALL和它的活动可能是由其他Zc-细胞因子增强。
BACKGROUND AND OBJECTIVES The identification of signals critical for the pathophysiology of T-cell acute lymphoblastic leukemia (T-ALL) should contribute to the development of novel, more effective therapeutic strategies. Common gamma-chain signaling cytokines (gammac-cytokines) - interleukins 2, 4, 7, 9 and 15 - differentially regulate T-cell development, survival, proliferation and differentiation. Although studies exist on some individual cytokines, no comprehensive analysis of the effects of the Zc-cytokine family on malignant T cells has been reported. Here, we examined the effect of Zc-cytokines on T-ALL proliferation. DESIGN AND METHODS Primary leukemic cells were collected at diagnosis from the blood or bone marrow of children with T-ALL. The cells were immunophenotyped and classified according to maturation stage. Proliferative responses to gammac-cytokines were assessed by 3H-thymidine incorporation. RESULTS All gammac-cytokines promoted proliferation of primary T-ALL cells. Interleukin (IL)-7 was the cytokine that most frequently induced leukemic cell proliferation and promoted the most robust responses. IL-4 preferentially stimulated proliferation of samples with a more mature immunophenotype, whereas CD1a-positive cortical T-ALL cells were less responsive to IL-9. Finally, combinations of two Zc-cytokines showed synergistic or additive proliferative effects. INTERPRETATION AND CONCLUSIONS This study indicates that all the gammac-cytokines tested can stimulate proliferation of leukemic T cells and suggests that synergistic effects may occur in vivo. We present the first demonstration that IL-9 and IL-15 can provide a proliferative signal to T-ALL cells. Importantly, our results support the hypothesis that IL-7 may function as a critical regulator of T-ALL and that its activity may be potentiated by other Zc-cytokines.