Significance of OCT1 Expression in Acute Myeloid Leukemia

Pathol Oncol Res. 2017 Jul;23(3):665-671. doi: 10.1007/s12253-016-0161-7. Epub 2016 Dec 26.

Abstract

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).

Keywords: Acute myeloid leukemia; OCT1; Resistance to chemotherapy.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, CD34 / genetics
  • Female
  • Humans
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / pathology
  • Male
  • Middle Aged
  • Octamer Transcription Factor-1 / genetics*
  • Prognosis
  • RNA, Messenger / genetics
  • Remission Induction
  • Young Adult

Substances

  • Antigens, CD34
  • Octamer Transcription Factor-1
  • POU2F1 protein, human
  • RNA, Messenger