Subsets of natural killer cells in chronic myeloid leukemia and their relation with some inflammatory cytokines

Abstract

As in other malignancies, different subsets of natural killer (NK) cells play a crucial role in the recognition and lysing of malignant cells in chronic myeloid leukemia (CML). This study aims to identify two subsets of NK, cytotoxic (cluster of differentiation [CD] 16+bright) and cytokine-producing NK (CD56+bright) in newly diagnosed CML patients. This study is conducted on 20 newly diagnosed Iraqi patients (12 males and 8 females) with CML, in chronic phase, at the age range of 17–55 years. Along with patients, 20 healthy subjects (with matched age and gender) were enrolled to act as a control group. To identify NK cells and their subsets in peripheral blood samples, the expression of CD45, CD3, CD56, and CD16 markers was evaluated by flow cytometry technique. Furthermore, the serum level of interferon gamma (IFN-γ) and interleukin (IL)-18 was determined by the enzyme-linked immunosorbent assay technique. The age of patients at the diagnosis of disease is (35.6 ± 12.2 years) and the male: female ratio was 1.5:1. The serum level of IL-18 in newly diagnosed CML patients (30.3 ± 6.5 pg/mL) was significantly (P < 0.0001) higher than those in control group (18.3 ± 7.8 pg/mL), while the serum levels of IFN-γ in newly diagnosed patients are significantly (P = 0.006) dropped down to (89.1 ± 7.2 pg/mL from that in control group (109.4 ± 30.3 pg/mL). The percentage of NK cells in newly diagnosed CML patients is significantly lower than in control group. There is a significant elevation in the cytotoxic NK cells (CD16+bright) subset, and a significant decrease in the cytokine-producing NK subset (CD56+bright) in newly diagnosed patients when compared to those in control group. Although there is an elevation in the percentage of cytotoxic NK cells (CD16+bright) subset of CML patients at the first diagnosis, these cells are not able to recognize and attack malignant cells, which may be due to low expression of their activating receptors and needs more investigation. Furthermore, present results found a low percentage of cytokine-producing NK cells (CD56+bright) and a low level of IFN-γ in CML patients, although there is an elevation in IL-18, which indicates that IL-18 may be not the main stimulator to these cells, so activation pathway of this subset of NK cells needs further investigation.