NK-Cell Receptor Repertoire in Chronic Myeloid Leukemia

BACKGROUND. Escape of leukemia cells from immune surveillance appears to be one of the most relevant areas in the study of resistance mechanisms in chronic myeloid leukemia (CML). AIM. To study the characteristics of the NK-cell immune response in patients with chronic phase (CP) CML on third-line therapy with tyrosine kinase inhibitors (TKIs) of the second generation. MATERIALS & METHODS. The study enrolled 40 CML CP patients receiving third-line therapy at the VA Almazov National Medical Research Center. The control group consisted of 20 healthy subjects (HS). The quantitative characteristics of NK- and TNK-cells as well as the expression of activating and inhibitory receptors on NK-cells were assessed using flow cytometry. KIR (Killer cell Immunoglobulin-like Receptors) haplotypes were analyzed by PCR and electrophoresis of PCR amplification products. RESULTS. Irrespective of treatment response, CML patients showed no significant differences regarding either the quantitative characteristics of NK- and TNK-cells or activating and inhibitory receptors on NK-cells. However, in the quantitative characteristics of inhibitory KIR alleles as well as in the expression of two activating KIR alleles (KIR2DS4 and KIR3DS1), significant differences were identified in HS vs. CML patients (p < 0.05). At the same time, the expression rate was similar in the groups with optimal response and therapy resistance (p = 0.25). There were also no significant differences in the rate of KIR haplotypes in HS and two groups of patients. In most CML patients as well as in HS, Bx haplotype of KIR was identified. The percentage of deaths was higher in the group with A haplotype (4/9; 45 %) vs. Bx haplotype (4/31; 13 %) (p = 0.008). The median progression-free survival (PFS) in the A haplotype subgroup was 76 (range 24–162) months vs. 69 (range 3–179) months in the Bx haplotype subgroup; the median overall survival (OS) was 69 (18–179) months vs. 76 (24–159) months, respectively. CONCLUSION. No significant differences were revealed in the expression of activating and inhibitory receptors on NK-cells in both groups of patients with response to TKI third-line therapy and therapy resistance compared to HS. This study demonstrated that NK-cell immune response had no effect on complete cytogenetic response. The results of the study suggest that the assessment of NK-cell immune response and KIR haplotypes cannot be regarded as a valuable tool for predicting the treatment efficacy in CML CP patients. However, due to heterogeneity of the groups under this study, further research is necessary to understand the prognostic value of KIR haplotypes in achieving response to therapy as well as their effect on OS and PFS.