Gene expression analysis of activating and inhibitory receptors of natural killer cells in patients with acute myeloblastic leukemia

Abstract

Purpose: Natural killer (NK) cells are cytotoxic lymphocytes, which have long been known to play an essential role in immune surveillance of tumor cells. The results of several clinical studies imply evidence of impaired activity of NK cells in acute myeloblastic leukemia (AML). The aim of this study was to investigate the gene expression of activating and inhibitory receptors of NK cells in patients with newly diagnosed AML before and after induction therapy using 7 + 3 regimen in comparison to healthy donors.

Materials and methods: Sixteen AML patients aged 16-64 years as well as 16 matched healthy individuals were studied. Peripheral blood samples from patients were obtained in two steps, namely, in newly diagnosed patients and 28 days after receiving induction therapy. Real-time PCR was performed to evaluate the expression levels of activating receptors, including DNAM-1 and NKp46 as well as inhibitory receptors of KIR2DL1 and NKG2A.

Results: Our results demonstrated that the newly diagnosed patients showed over 50% decrease in NKp46 expression and a 6-fold increase in KIR2DL1 expression compared to healthy controls. The mRNA expression analysis in patients after induction therapy suggested a significant decrease in mRNA expressions of KIR2DL1 and NKG2A in comparison to newly diagnosed patients.

Conclusion: Herewith, we show a statistical difference in mRNA expression levels of activating (NKp46) and inhibitory receptors from NK cells in newly diagnosed AML patients when compared with healthy controls or patients who received induction therapy, supporting the findings of researchers who reported the impaired NK cells cytotoxicity in AML patients.

Keywords: Acute myeloid leukemia; Gene expression; NK cell Receptors; NK cells.