Karauzum Sibel Berker, Yasar Duygu, Dirice Ercument, Imir Nilufer, Luleci Guven, Ozes Osman Nidai
Department of Medical Biology and Genetics, Akdeniz University, Antalya, Turkey.
Growth Factors. 2007 Apr;25(2):94-100. doi: 10.1080/08977190701345515.
Hairy cell leukemia (HCL) is a chronic B-cell lymphoproliferative disorder with pathological manifestations usually including splenomegaly and pancytopenia. Interferons (IFNs), specifically of the alpha subtypes, have shown a significant anti-tumor effect in HCL patients, with improvement of hematological parameters within the first few months of treatment. However, the therapeutic effect of IFN-alpha is still rather limited. The mechanisms responsible for the beneficial action of IFN-alpha in HCL patients are unclear. A continuous line of cells (Eskol) from a patient diagnosed with HCL was established and shown to have several properties of HCL. Even though, Eskol cells are very resistant to anti-proliferative activity of IFN-alpha, Daudi cells, another human B-cell-derived cell line, are very sensitive to anti-proliferative activity of IFN-alpha and are commonly used as a model cell to test anti-proliferative effect of IFN-alpha. To understand the molecular reason(s) behind the observed obvious differences to IFN sensitivity of above cells, we have analyzed the expression levels of BCL2, caspase-1, Laminin and PARP in these cells. We found that Daudi cells do not express BCL2 at all, and probably because of that, these cells have constantly cleaved, and probably activated form of caspase-1. However, when we over-expressed BCL2 in these cells, they lost processed form of caspase-1 and became resistant to anti-proliferative activity of IFN-alpha. These results let us to suggest that IFN-alpha sensitivity of B-cell lymphomas, once again, depends on the presence or absence of BCL2.
毛细胞白血病（HCL）是一种慢性B细胞淋巴增殖性疾病，其病理表现通常包括脾肿大和全血细胞减少。干扰素（IFN），特别是α亚型干扰素，在HCL患者中显示出显著的抗肿瘤作用，在治疗的最初几个月内血液学参数得到改善。然而，α干扰素的治疗效果仍然相当有限。α干扰素在HCL患者中产生有益作用的机制尚不清楚。建立了一株来自一名诊断为HCL患者的连续细胞系（Eskol），并显示其具有HCL的多种特性。尽管Eskol细胞对α干扰素的抗增殖活性非常耐药，但另一种人B细胞来源的细胞系Daudi细胞对α干扰素的抗增殖活性非常敏感，常用于测试α干扰素的抗增殖作用的模型细胞。为了了解上述细胞对IFN敏感性存在明显差异背后的分子原因，我们分析了这些细胞中BCL2、半胱天冬酶-1、层粘连蛋白和PARP的表达水平。我们发现Daudi细胞根本不表达BCL2，可能正因如此，这些细胞持续裂解，可能是半胱天冬酶-1的活化形式。然而，当我们在这些细胞中过表达BCL2时，它们失去了半胱天冬酶-1的加工形式，并对α干扰素的抗增殖活性产生耐药性。这些结果使我们认为，B细胞淋巴瘤对α干扰素的敏感性再次取决于BCL2的有无。
