Damiani D, Michieli M, Michelutti A, Fanin R, Russo D, Baccarani M
Department of Morphologic and Clinical Research, Udine University School of Medicine, Italy.
Leuk Lymphoma. 1995 Apr;17(3-4):289-94. doi: 10.3109/10428199509056834.
Chronic myeloid leukaemia (CML) is a well known model of a disease refractory to chemotherapy, including anthracyclines and other drugs that are believed to be pumped out of the cells by a 170 Kd transmembrane glycoprotein (P170). In 35 cases of Ph+ CML we investigated the reactivity of leukaemic cells to a P170-directed monoclonal antibody (MRK-16), by means of flow cytometry. P170 overexpression was found in 4/14 (29%) chronic phase CML cases and in 16/23 (70%) accelerated and blastic phase CML cases (P = 0.01). The same cells were assayed for their ability to retain Daunorubicin and Idarubicin after 2-hours in vitro incubation with 1000 ng/ml of either drug. It was found that anthracycline cell concentration was negatively related with the degree of the reactivity to MRK-16. In accelerated and blastic phase, CML cells simultaneously expressed P170 and the stem cell related marker, CD34. These data confirm that Ph+ leukaemic cells overexpress P170, show that P170 overexpression is functionally relevant, and suggest that P170-related multidrug resistance may be an important factor for chemotherapy failure in Ph+ CML.
慢性粒细胞白血病（CML）是一种众所周知的对化疗耐药的疾病模型，包括对蒽环类药物和其他据信由一种170千道尔顿跨膜糖蛋白（P170）从细胞中泵出的药物耐药。在35例Ph+慢性粒细胞白血病患者中，我们通过流式细胞术研究了白血病细胞对一种针对P170的单克隆抗体（MRK-16）的反应性。在4/14（29%）的慢性期慢性粒细胞白血病病例和16/23（70%）的加速期及急变期慢性粒细胞白血病病例中发现了P170的过表达（P = 0.01）。在用1000纳克/毫升的柔红霉素或伊达比星进行2小时体外孵育后，对相同的细胞检测其保留这些药物的能力。发现蒽环类药物在细胞中的浓度与对MRK-16的反应程度呈负相关。在加速期及急变期，慢性粒细胞白血病细胞同时表达P170和干细胞相关标志物CD34。这些数据证实Ph+白血病细胞过表达P170，表明P170过表达在功能上具有相关性，并提示与P170相关的多药耐药可能是Ph+慢性粒细胞白血病化疗失败的一个重要因素。
