Abstract

The coagulation system is regularly activated in patients with acute leukemia, especially with acute promyelocytic leukemia. Up to 30% of these patients suffer from thromboembolic complications. Obviously, activation of thrombin occurs in the natural course of cancer. During tumor progression, many patients develop coagulation disorders; treatment is complicated by increased resistance of tumor cells to chemotherapy. Thrombin-mediated activation of cellular receptor(s), such as proteinase-activated receptor-1(PAR-1), plays an important role in tumor growth, local progression, and distant metastasis. Our hypothesis is, that leukemia cells that express PAR-1 have a survival benefit if they are activated by thrombin.We harvested HL-60 cells in vitro. We detected PAR-1 expression using reverse transcription-polymerase chain reaction (RT-PCR) and fluorescence activated cell sorting (FACS) scan.We found that HL-60 cells expressed PAR-1 receptor. Furthermore,we employed a series of different concentrations of thrombin into the HL-60 cell culture system.With certain interval of low level of thrombin, HL-60 cell growth was enhanced,in contrast, we found that HL-60 cell apoptosis was observed under higher concentration of thrombin.In summary, we found that human leukemia HL-60 cell exhibits a positive PAR-1 expression. Also, thrombin could influence the growth of HL-60 mediated by PAR-1 possibly. Further experiments will show if these cell-biological mechanisms aggravate cellular proliferation/apoptosis in leukemia cells. Therapeutic consequences, such as therapeutic thrombin inhibition in addition to chemotherapy are discussed.

Disclosure: No relevant conflicts of interest to declare.

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