Luchetti F, Gregorini A, Papa S, Burattini S, Canonico B, Valentini M, Falcieri E
Istituto di Scienze Morfologiche, Università di Urbino, Italy.
Haematologica. 1998 Nov;83(11):974-80.
The K562 cell line, derived from a chronic myeloid leukemia (CML) patient and expressing B3A2 bcr-abl hybrid gene, is known to be particularly resistant to apoptotic death. IFN-alpha treatment of CML patients impairs malignant cell clone, apparently protecting from progression to terminal blast crisis. The mechanisms underlying this kind of cell deletion are analyzed here by multiple technical approaches.
K562 cells, variably treated with IFN-alpha, were examined by agarose gel DNA electrophoresis, light and electron microscopy. The presence of bcr-abl rearrangement was revealed by RT-PCR.
At 4 day treatment both DNA ladder and apoptotic nuclear changes were identified, consistently in the presence of bcr-abl expression.
Even cells expressing bcr-abl, such as K562, can be triggered to apoptosis. Therefore, this genetic condition, commonly preventing PCD, does not prevent IFN-alpha-mediated apoptosis. PCD seems thus to be the mechanism underlying IFN-alpha-treated K562 cell deletion and it could be the basis of malignant clone reduction in IFN-alpha treated CML patients.
K562细胞系源自一名慢性粒细胞白血病（CML）患者，表达B3A2 bcr-abl融合基因，已知其对凋亡性死亡具有特别的抗性。用α干扰素治疗CML患者可损害恶性细胞克隆，显然能防止病情发展至终末期原始细胞危象。本文采用多种技术方法分析了这种细胞缺失的潜在机制。
用α干扰素对K562细胞进行不同处理，通过琼脂糖凝胶DNA电泳、光学显微镜和电子显微镜进行检测。通过逆转录聚合酶链反应（RT-PCR）检测bcr-abl重排的存在情况。
在4天的处理后，在存在bcr-abl表达的情况下，一致观察到DNA梯状条带和凋亡性核变化。
即使是表达bcr-abl的细胞，如K562细胞，也可被诱导发生凋亡。因此，这种通常会阻止程序性细胞死亡（PCD）的遗传状态，并不能阻止α干扰素介导的凋亡。程序性细胞死亡似乎是α干扰素处理的K562细胞缺失的潜在机制，并且可能是α干扰素治疗的CML患者恶性克隆减少的基础。
