Park Sang Hyuk, Park Chan-Jeoung, Kim Dae-Young, Lee Bo-Ra, Kim Young Jin, Cho Young-Uk, Jang Seongsoo
Department of Laboratory Medicine, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Republic of Korea; Department of Laboratory Medicine, Pusan National University School of Medicine, Pusan National University Hospital, Biomedical Research Institute, Pusan National University Hospital, Busan, South Korea.
Department of Laboratory Medicine, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Republic of Korea.
Leuk Res. 2015 Oct;39(10):1109-16. doi: 10.1016/j.leukres.2015.07.006. Epub 2015 Jul 23.
We evaluated the ability of the rhodamine-123 efflux assay, multidrug resistance-associated protein-1 (MRP1) expression assay and P-glycoprotein (Pgp) expression assay to discriminate chronic myelogenous leukemia (CML) patients who had failed treatment or were at risk of failure. Each assay was performed in blood samples from CML patients (n=224) treated with tyrosine kinase inhibitors, taken at diagnosis (n=14) and follow-up (n=210). Patient samples were categorized as optimal response (n=120), suboptimal response (n=54), and treatment failure (n=36). Treatment-failed patients had a significantly higher MRP1 expression (5.24% vs. 3.54%, P=0.006) and Pgp expression (5.25% vs. 3.48%, P=0.005) than responders. Both MRP1 (%) and Pgp (%) were highly specific (95.2% and 94.5%) and relatively accurate (83.0% and 82.5%) in the detection of treatment non-responders. Of treatment-failed patients, 41.2% had a positive result in at least one assay and of these patients without ABL1 kinase domain mutation, 51.9% were positive in at least one assay. However, the rhodamine-123 efflux assay failed to discriminate two patient groups. Thus, both MRP1 and Pgp expression assays could be useful for additional identification of treatment non-responders in CML patients without ABL1 mutation.
我们评估了罗丹明 - 123外排试验、多药耐药相关蛋白1（MRP1）表达试验和P - 糖蛋白（Pgp）表达试验鉴别治疗失败或有失败风险的慢性髓性白血病（CML）患者的能力。每项试验均在接受酪氨酸激酶抑制剂治疗的CML患者（n = 224）的血样中进行，血样采集于诊断时（n = 14）和随访时（n = 210）。患者样本分为最佳反应组（n = 120）、次优反应组（n = 54）和治疗失败组（n = 36）。治疗失败的患者的MRP1表达（5.24% 对3.54%，P = 0.006）和Pgp表达（5.25% 对3.48%，P = 0.005）显著高于反应者。MRP1（%）和Pgp（%）在检测治疗无反应者方面具有高度特异性（分别为95.2%和94.5%）和相对准确性（分别为83.0%和82.5%）。在治疗失败的患者中，41.2%在至少一项试验中呈阳性，在这些没有ABL1激酶结构域突变的患者中，51.9%在至少一项试验中呈阳性。然而，罗丹明 - 123外排试验未能区分两组患者。因此，MRP1和Pgp表达试验都有助于在没有ABL1突变的CML患者中进一步识别治疗无反应者。
