Ozes O N, Klein S B, Reiter Z, Taylor M W
Department of Biology, Indiana University, Bloomington 47405.
Leuk Res. 1993 Nov;17(11):983-90. doi: 10.1016/0145-2126(93)90046-n.
The B-lymphoblastoid cell line Eskol, which is composed of differentiated cells resembling hairy-cell leukemia, has been used to study the effects of type I interferon in vitro. In order to study the mechanism of delayed interferon therapy resistance, a hairy-cell leukemia-like clonal cell line (IREs-4) was isolated from Eskol after 4 months of exposure to r-metIFN-con1. When compared to Eskol cells, the IREs-4 cells were resistant to the antiproliferative effect of type I interferons as well as interferon induced protection against LAK cells. Treatment of IREs-4 with type I interferon did not induce MHC antigens, although both MHC class I and II antigens were induced in Eskol. Binding studies indicated the presence of equal numbers of high affinity binding sites with similar affinities on both cell lines. The resistant phenotype appears to result from an intracellular event which is essential to interferon signal transduction. It is hypothesized that this variant may reflect heterogeneity in the normal population of hairy-cell leukemia cells, and may explain the partial resistance of HCL patients to IFN therapy.
B淋巴母细胞系Eskol由类似于毛细胞白血病的分化细胞组成，已被用于体外研究I型干扰素的作用。为了研究干扰素治疗延迟耐药的机制，在暴露于重组人干扰素α-1（r-metIFN-con1）4个月后，从Eskol中分离出一种毛细胞白血病样克隆细胞系（IREs-4）。与Eskol细胞相比，IREs-4细胞对I型干扰素的抗增殖作用以及干扰素诱导的针对LAK细胞的保护作用具有抗性。用I型干扰素处理IREs-4不会诱导MHC抗原，尽管在Eskol中MHC I类和II类抗原均被诱导。结合研究表明，两种细胞系上存在数量相等、亲和力相似的高亲和力结合位点。耐药表型似乎是由细胞内事件导致的，这一事件对干扰素信号转导至关重要。据推测，这种变体可能反映了毛细胞白血病细胞正常群体中的异质性，并可能解释HCL患者对IFN治疗的部分耐药性。
