Begleiter A, Goldenberg G J, Anhalt C D, Lee K, Mowat M R, Israels L G, Johnston J B
Department of Internal Medicine, University of Manitoba, Canada.
Leuk Res. 1991;15(11):1019-27. doi: 10.1016/0145-2126(91)90107-5.
The postulated biochemical mechanisms responsible for clinical resistance to chlorambucil (CLB) in chronic lymphocytic leukemia (CLL) have been examined. The total sulfhydryl, non-protein-bound sulfhydryl, protein-bound sulfhydryl (PSH) and glutathione (GSH) levels, in addition to glutathione S-transferase (GST) activities, were measured in the leukemic cells of 18 CLL patients. In addition, the formation and repair of DNA cross-links were measured following incubation of the cells with 100 microM chlorambucil in vitro. These parameters were then correlated with the subsequent clinical responses of the patients, as measured by the percent fall in lymphocyte count 3 weeks following 0.9 mg/kg chlorambucil. No correlations were observed between any of the individual parameters and clinical response, although a slight positive correlation was observed between the PSH:GSH ratio and clinical response. These findings suggest that multiple mechanisms may contribute to CLB-resistance in CLL.
对慢性淋巴细胞白血病（CLL）中与苯丁酸氮芥（CLB）临床耐药相关的假定生化机制进行了研究。测定了18例CLL患者白血病细胞中的总巯基、非蛋白结合巯基、蛋白结合巯基（PSH）和谷胱甘肽（GSH）水平，以及谷胱甘肽S-转移酶（GST）活性。此外，在体外将细胞与100μM苯丁酸氮芥孵育后，测定DNA交联的形成和修复情况。然后将这些参数与患者随后的临床反应相关联，临床反应通过给予0.9mg/kg苯丁酸氮芥3周后淋巴细胞计数下降的百分比来衡量。尽管观察到PSH:GSH比值与临床反应之间存在轻微正相关，但未观察到任何单个参数与临床反应之间的相关性。这些发现表明，多种机制可能导致CLL对苯丁酸氮芥产生耐药性。
