Shimoyama M, Ohtsu T, Ishida Y, Kuroki Y, Shimada Y, Tobinai K, Minato K, Hamada H, Tsuruo T
Hematology-Oncology and Clinical Cancer Chemotherapy Division, National Cancer Center Hospital.
Gan To Kagaku Ryoho. 1988 Oct;15(10):2863-70.
Two monoclonal antibodies, MRK16 and MRK20 that recognize P-glycoprotein and P-85 kd protein on the surface of adriamycin (ADM) resistant cells, respectively, were tested for the reactivity with 40 cultured leukemia/lymphoma cell lines. F(ab')2 form is essential to avoid false reaction through Fc gamma-R. Drug sensitivity of 19 representative cell lines were also examined in vitro. From this study, it was found that these cell lines were classified into 4 groups. Group 1 (4 cell lines) was insensitive to ADM, mitoxantron (MXT), etoposide (VP-16) and vincristine (VCR), and reactive to MRK16 and MRL20. Group II (1 cell line) was insensitive to the 4 drugs, but not reactive to both antibodies. Group III (3 cell lines) was insensitive to ADM, MXT and VP-16, but sensitive to VCR, and reactive to MRK20, but not to MRK16. Group IV (all other cell lines) was sensitive to these drugs, and not reactive to both antibodies. From these results, MRK16 detects P-glycoprotein-associated multidrug resistance (MDR), while MRK20 does P 85-kd-associated another type MDR (cross resistance to ADM, MXT and VP-16, but not to VCR). MRK20 reacted with monocytes, but MRK16 did not with any WBC type. One hundred and ninety eight clinical samples obtained from blood cancer were tested for the reactivity with MRK16. MRK16 did not react with any of 98 samples obtained before treatment, but did with 9 of 100 obtained at relapse or refractory stage after chemotherapy. The results indicate that MRK16 is useful to detect drug resistance phenotype of leukemia and lymphoma.
两种单克隆抗体MRK16和MRK20,分别识别阿霉素(ADM)耐药细胞表面的P-糖蛋白和P-85 kd蛋白,检测它们与40种培养的白血病/淋巴瘤细胞系的反应性。F(ab')2形式对于避免通过Fcγ-R产生假反应至关重要。还对19种代表性细胞系的药物敏感性进行了体外检测。从这项研究中发现,这些细胞系分为4组。第1组(4种细胞系)对ADM、米托蒽醌(MXT)、依托泊苷(VP-16)和长春新碱(VCR)不敏感,对MRK16和MRL20有反应。第II组(1种细胞系)对这4种药物不敏感,但对两种抗体均无反应。第III组(3种细胞系)对ADM、MXT和VP-16不敏感,但对VCR敏感,对MRK20有反应,但对MRK16无反应。第IV组(所有其他细胞系)对这些药物敏感,对两种抗体均无反应。从这些结果来看,MRK16检测与P-糖蛋白相关的多药耐药(MDR),而MRK20检测与P 85-kd相关的另一种类型的MDR(对ADM、MXT和VP-16交叉耐药,但对VCR不耐药)。MRK20与单核细胞反应,但MRK16与任何白细胞类型均无反应。对198份从血癌患者获得的临床样本检测其与MRK16的反应性。MRK16与98份治疗前获得的样本均无反应,但与化疗后复发或难治阶段获得的100份样本中的9份有反应。结果表明,MRK16有助于检测白血病和淋巴瘤的耐药表型。