Sacha Tomasz, Czekalska Sylwia, Foryciarz Kajetana, Zawada Magdalena, Florek Izabela, Cwynar Dorota, Wator Gracjan, Balwierz Walentyna, Skotnicki Aleksander B
Katedra i Klinika Hematologii, Collegium Medicum UJ w Krakowie.
Przegl Lek. 2011;68(4):191-5.
Chronic myeloid leukemia is a clonal disorder caused by formation of chimeric BCR/ABL gene and bcr/abl protein with abnormally high tyrosine kinase activity. The use of imatinib--the first tyrosine kinase inhibitor results in achievement of hematologic, cytogenetic and molecular response in majority of patients. However despite its high efficacy not all patients respond to imatinib, whereas others lose an initial response. Imatinib is a substrate of human organic cation transporter-1 (hOCT1), which actively delivers the drug into the cells, and efflux transporters. To identify potential imatinib failures, we investigated the expression of hOCT1 using real-time quantitative reverse transcription-polymerase chain reaction (RQ-PCR) in 155 CML patients. Patients with low pretreatment hOCT1 expression had inferior major and complete molecular response (MMR and CMR) rates (p = 0.0001, p = 0.0001) achieved any time or at 18 months of imatinib treatment (p = 0.023, p = 0.022). The expression of hOCT1 is important in determining the clinical response to imatinib. The analysis of hOCT1 expression by RQ-PCR is convenient and clinically available, and the results could help in introduction of optimal first line therapy in CML patients.
慢性髓性白血病是一种由嵌合性BCR/ABL基因和具有异常高酪氨酸激酶活性的bcr/abl蛋白形成所导致的克隆性疾病。使用伊马替尼——首个酪氨酸激酶抑制剂,可使大多数患者实现血液学、细胞遗传学和分子反应。然而,尽管其疗效显著,但并非所有患者都对伊马替尼有反应,而其他患者则会失去初始反应。伊马替尼是人类有机阳离子转运体-1(hOCT1)的底物,hOCT1可将药物主动转运至细胞内,同时它也是一种外排转运体。为了识别潜在的伊马替尼治疗失败情况,我们使用实时定量逆转录-聚合酶链反应(RQ-PCR)对155例慢性髓性白血病患者的hOCT1表达进行了研究。预处理时hOCT1表达较低的患者,在伊马替尼治疗的任何时间或18个月时,主要分子反应和完全分子反应(MMR和CMR)率均较差(p = 0.0001,p = 0.0001)(p = 0.023,p = 0.022)。hOCT1的表达对于确定伊马替尼的临床反应很重要。通过RQ-PCR分析hOCT1表达简便且临床可用,其结果有助于为慢性髓性白血病患者引入最佳的一线治疗方案。