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重组干扰素α在淋巴增殖性疾病患者中的临床反应与结合的关系。

Relationship of the clinical response and binding of recombinant interferon alpha in patients with lymphoproliferative diseases.

作者信息

Faltynek C R, Princler G L, Rossio J L, Ruscetti F W, Maluish A E, Abrams P G, Foon K A

出版信息

Blood. 1986 Apr;67(4):1077-82.

PMID:2937469
Abstract

Patients with hairy cell leukemia (HCL) and chronic lymphocytic leukemia (CLL) were treated with recombinant interferon alpha A (rIFN-alpha A). The binding of iodinated recombinant interferon-alpha to baseline samples of peripheral blood mononuclear cells (PBMCs) from the leukemia patients was compared with clinical responsiveness to rIFN-alpha A. HCL patients (8/10) responded to rIFN-alpha A therapy, whereas none (0/10) of the CLL patients studied responded. The PBMCs from the eight responsive HCL patients bound approximately twice as much iodinated interferon as the PBMCs from nonresponsive CLL patients. This difference was due to more high-affinity receptors per cell with no difference in the affinity of the interferon-receptor interaction. However, because PBMCs from HCL patients were larger than PBMCs from CLL patients, the cell surface receptor density was similar. The leukemic cells from one of the two nonresponsive HCL patients bound iodinated interferon similarly to the cells from the responsive HCL patients, whereas the leukemic cells from the other nonresponsive HCL patient bound considerably less. The rapidity of response of the HCL patients did not correlate with the level of binding of iodinated interferon. Our results suggest that the absolute number of interferon receptors per cell may be only one of several important parameters in the response to rIFN-alpha A therapy, and that the responsiveness of a particular lymphoproliferative disease or a particular patient to rIFN-alpha A therapy cannot be predicted or explained solely by the degree of interaction between IFN and its cell surface receptor.

摘要

毛细胞白血病(HCL)和慢性淋巴细胞白血病(CLL)患者接受了重组干扰素αA(rIFN-αA)治疗。将碘化重组干扰素-α与白血病患者外周血单个核细胞(PBMC)的基线样本的结合情况与对rIFN-αA的临床反应性进行了比较。HCL患者(8/10)对rIFN-αA治疗有反应,而所研究的CLL患者无一(0/10)有反应。8例有反应的HCL患者的PBMC结合的碘化干扰素量约为无反应的CLL患者的PBMC的两倍。这种差异是由于每个细胞的高亲和力受体更多,而干扰素-受体相互作用的亲和力没有差异。然而,由于HCL患者的PBMC比CLL患者的PBMC大,细胞表面受体密度相似。两名无反应的HCL患者中一名患者的白血病细胞结合碘化干扰素的情况与有反应的HCL患者的细胞相似,而另一名无反应的HCL患者的白血病细胞结合的量则少得多。HCL患者的反应速度与碘化干扰素的结合水平无关。我们的结果表明,每个细胞的干扰素受体绝对数量可能只是对rIFN-αA治疗反应的几个重要参数之一,并且特定的淋巴增殖性疾病或特定患者对rIFN-αA治疗的反应性不能仅通过IFN与其细胞表面受体之间的相互作用程度来预测或解释。

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Relationship of the clinical response and binding of recombinant interferon alpha in patients with lymphoproliferative diseases.重组干扰素α在淋巴增殖性疾病患者中的临床反应与结合的关系。
Blood. 1986 Apr;67(4):1077-82.
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