Biochemistry Department, National Research Centre, Cairo, Egypt.
Med Oncol. 2011 Dec;28 Suppl 1:S471-5. doi: 10.1007/s12032-010-9661-6. Epub 2010 Aug 31.
Evidence indicates that the slowly expanding population of B cells that characterizes chronic lymphocytic leukemia (CLL) results primarily from defects in responses to cytokines. We evaluated the prognostic value of soluble CD44 and IFN-γ in B-cell chronic lymphocytic leukemia (B-CLL) and analyzed their source and regulation secretion in B-CLL clones in vitro. Levels of soluble CD44 standard (sCD44s) and IFN-γ were analyzed by enzyme-linked immunosorbent assay. B-CLL cells were separated and stimulated in vitro for the detection of both markers. Serum levels of sCD44s and IFN-γ were significantly elevated in patients with B-CLL in comparison with normal persons. Elevated levels of sCD44s and IFN-γ were associated with an advanced disease as reflected by increased values as stage progress. In B-CLL, sCD44s as well as IFN-γ was shed from leukemia cells as shown by in vitro cultures. Stimulation of B-CLL clones results in a proliferation-associated increased secretion of sCD44s and IFN-γ. B-CLL clones from advanced-stage patients are characterized by an increased capacity for proliferation and production of both markers in comparison with early-stage patients. Our present results suggest that sCD44 and IFN-γ may be of major importance in the pathogenesis of B-CLL, and inhibition of the effects of sCD44 and IFN-γ could be a potential therapeutic strategy.
证据表明，慢性淋巴细胞白血病（CLL）中特征性的 B 细胞缓慢扩增主要是由于对细胞因子反应的缺陷所致。我们评估了可溶性 CD44 和 IFN-γ 在 B 细胞慢性淋巴细胞白血病（B-CLL）中的预后价值，并分析了它们在体外 B-CLL 克隆中的来源和调节分泌。通过酶联免疫吸附试验分析可溶性 CD44 标准（sCD44s）和 IFN-γ 的水平。分离 B-CLL 细胞并进行体外刺激以检测这两种标志物。与正常人相比，B-CLL 患者的血清 sCD44s 和 IFN-γ 水平显著升高。升高的 sCD44s 和 IFN-γ 水平与疾病的进展有关，表现为随着分期的进展而增加。在 B-CLL 中，sCD44s 和 IFN-γ 均从白血病细胞脱落，如体外培养所示。B-CLL 克隆的刺激导致与增殖相关的 sCD44s 和 IFN-γ 的分泌增加。与早期患者相比，晚期患者的 B-CLL 克隆增殖能力和两种标志物的产生能力均增加。我们目前的结果表明，sCD44 和 IFN-γ 可能在 B-CLL 的发病机制中具有重要意义，抑制 sCD44 和 IFN-γ 的作用可能是一种潜在的治疗策略。
