Kolesnikova Maria, Sen'kova Aleksandra, Tairova Sofia, Ovchinnikov Viktor, Pospelova Tatiana, Zenkova Marina
Department of therapy, hematology and transfusiology, Novosibirsk State Medical University, Krasny Prospect 52, 630091 Novosibirsk, Russia.
Laboratory of nucleic acids biochemistry, Institute of Chemical Biology and Fundamental Medicine SB RAS, Lavrentieva ave. 8, 630090 Novosibirsk, Russia.
J Pers Med. 2019 May 7;9(2):24. doi: 10.3390/jpm9020024.
Multidrug resistance (MDR) is a major challenge in leukemia treatment. The objective of this study was to identity predictors of MDR to allow for rapid and economical assessment of the efficacy of planned antitumor therapy for leukemia patients. The study included 113 patients with acute and chronic leukemias. Prior to antitumor therapy, we measured the sensitivity of tumor cells of patients to the panel of chemotherapeutic drugs, together with mRNA and P-glycoprotein (P-gp) expression as one of the mechanisms of MDR, and compared these data with the response to therapy. The scales for leukemia patients according to therapy response, drug sensitivity of tumor cells, mRNA and P-gp levels, and the presence of unfavorable immunological and cytogenetic markers were introduced for subsequent correlation analysis. We show that the drug resistance of tumor cells of leukemia patients estimated in vitro at diagnosis correlates with a poor response to chemotherapy and is usually combined with aberrant and immature immunological markers, cytogenetic abnormalities, and a high expression of mRNA and P-gp. All together, these factors indicate unfavorable prognosis and low survival of leukemia patients. Thus, the sensitivity of tumor cells to chemotherapeutic drugs measured in vitro at diagnosis may have prognostic value for individual types of leukemia.
多药耐药(MDR)是白血病治疗中的一项重大挑战。本研究的目的是确定多药耐药的预测指标,以便能够快速且经济地评估针对白血病患者的计划抗肿瘤治疗的疗效。该研究纳入了113例急性和慢性白血病患者。在抗肿瘤治疗前,我们测定了患者肿瘤细胞对一组化疗药物的敏感性,以及作为多药耐药机制之一的mRNA和P-糖蛋白(P-gp)表达,并将这些数据与治疗反应进行比较。引入了根据治疗反应、肿瘤细胞药物敏感性、mRNA和P-gp水平以及不良免疫和细胞遗传学标志物的存在情况对白血病患者进行的评分,用于后续的相关性分析。我们发现,在诊断时体外评估的白血病患者肿瘤细胞耐药性与化疗反应不佳相关,并且通常与异常和不成熟的免疫标志物、细胞遗传学异常以及mRNA和P-gp的高表达相结合。所有这些因素均表明白血病患者预后不良且生存率低。因此,在诊断时体外测定的肿瘤细胞对化疗药物的敏感性可能对个别类型的白血病具有预后价值。