Stefanko Ewa, Rybka Justyna, Jaźwiec Bożena, Haus Olga, Stąpor Sylwia, Kuliczkowski Kazimierz, Wróbel Tomasz
Department of Hematology, Blood Neoplasms and Bone Marrow Transplantation, Wrocław Medical University, Wrocław, Poland.
Department of Clinical Genetics, Collegium Medicum Nicolaus Copernicus University, Bydgoszcz, Poland.
Pathol Oncol Res. 2017 Jul;23(3):665-671. doi: 10.1007/s12253-016-0161-7. Epub 2016 Dec 26.
Organic cation transporter 1 (OCT1) is one of the membrane proteins in the large solute carrier (SLC) family. It participates in the transport of organic cations, i.e. nutrients, neurotransmitters, metabolites or drugs in an electrogenic manner and translocate various cationic cytostatics. Knowledge concerning the expression of drug transporters in tumor cells may help to develop cytotoxic agents that are targeted to specific tumors. OCT1 expression and its relationship to the proliferation of cancer cells, development of metastases and resistance to chemotherapy has been observed in solid tumors. There is no data concerning the significance of OCT1 expression in the clinical course and treatment results in acute myeloid leukemia (AML). The objective of the study was firstly to evaluate OCT1 mRNA expression in patients with newly diagnosed de novo AML, and secondly to compare the obtained results to the healthy control group as well as analyze them according to leukemia subtypes, CD34 expression, cytogenetic and molecular factors and treatment results. 101 patients with AML, excluding the subtype classified as M3 by French-American-British (FAB) criteria, were analyzed. The control group consisted of 26 healthy individuals. The evaluated material was bone marrow (BM). Real-time quantitative polymerase chain reaction (RQ-PCR) was used in the study as a method of evaluating OCT1 mRNA expression. The study showed a statistically significant lower expression of OCT1 mRNA in patients with AML in comparison to the control group. The level of OCT1 mRNA expression was lowest for CD34+ leukemia. No significant correlation between OCT1 mRNA expression and cytogenetic and molecular factors was observed. A significant influence of OCT1 mRNA expression on the clinical outcome of the disease was observed: patients with lower expression had higher chances of achieving complete remission (CR) and longer overall survival (OS).
有机阳离子转运体1(OCT1)是大溶质载体(SLC)家族中的膜蛋白之一。它以电生方式参与有机阳离子(即营养物质、神经递质、代谢物或药物)的转运,并转运各种阳离子细胞毒性药物。了解药物转运体在肿瘤细胞中的表达情况可能有助于开发针对特定肿瘤的细胞毒性药物。在实体瘤中已观察到OCT1的表达及其与癌细胞增殖、转移发展和化疗耐药性的关系。目前尚无关于OCT1表达在急性髓系白血病(AML)临床病程和治疗结果中的意义的数据。本研究的目的一是评估新诊断的初发AML患者中OCT1 mRNA的表达,二是将所得结果与健康对照组进行比较,并根据白血病亚型、CD34表达、细胞遗传学和分子因素以及治疗结果进行分析。对101例AML患者进行了分析,排除了法国-美国-英国(FAB)标准分类为M3的亚型。对照组由26名健康个体组成。评估的材料为骨髓(BM)。本研究采用实时定量聚合酶链反应(RQ-PCR)作为评估OCT1 mRNA表达的方法。研究表明,与对照组相比,AML患者中OCT1 mRNA的表达在统计学上显著降低。CD34+白血病患者的OCT1 mRNA表达水平最低。未观察到OCT1 mRNA表达与细胞遗传学和分子因素之间的显著相关性。观察到OCT1 mRNA表达对疾病临床结局有显著影响:表达较低的患者实现完全缓解(CR)的机会更高,总生存期(OS)更长。