Killer-cell immunoglobulin-like receptor genotype and haplotype combinations in children treated for acute lymphoblastic leukemia

Abstract

Introduction: Acute lymphoblastic leukemia (ALL) is the most common malignancy diagnosed in children. The factors predisposing to ALL remain mostly unknown. Natural killer (NK) cells are a component of innate immunity. Their role is to eliminate cells that were infected with viruses or underwent a neoplastic transformation. The activity of NK cells is regulated by their activating and inhibitory receptors, inter alia killer-cell immunoglobulin-like receptors (KIRs). The available data about a link between the incidence of ALL and KIR genotype are highly inconclusive, and further research is needed to explain whether such a relationship truly exists. The aim of this study was to analyze KIR genotype and haplotype combinations in children treated for ALL.

Material and methods: The study included 49 children diagnosed with ALL at 1.2-19.8 years of age. The control group was composed of 43 healthy subjects aged between 1.2 and 21.9 years. DNA was isolated using QIAamp DNA Mini kits. KIR genotypes were identified by a polymerase chain reaction (PCR) with sequence-specific primers (SSPs). The analysis also included KIR haplotype combinations: AA, AB and BB.

Results: Patients with ALL and controls did not differ significantly in the frequencies of individual KIR genes and haplotypes. However, the overall frequency of all 6 activating KIR genes in patients with ALL was significantly higher than in the controls (24.5% vs. 4.7%, p = 0.019).

Conclusions: The findings presented here imply that individual KIR genes do not play a significant role in the pathogenesis of ALL. Nevertheless, a higher number of activating KIR genes may constitute a risk factor for this malignancy.

Keywords: ALL; NK cells; killer immunoglobulin-like receptors (KIRs).

Fig. 1

Representative electrophoretogram of KIR genes on an agarose-coated plate. Numbers of stripes correspond to the following genes: 1 – 2DL1, 2 – 2DL2, 3 – 2DL3, 4 – 2DL4, 5 – 2DL5 all, 6 – 2DL5A, 7 – 2DL5B, 8 – 2DS1, 9 – 2DS2, 10 – 2DS3, 11 – 2DS4del, 12 – 2DS4ins, 13 – 2DS5, 14 – 3DL1, 15 – 3DL2, 16 – 3DL3, 17 – 3DS1, 18 – 2DP1, 19 – 3DP1, 20 – DNA contamination control, 21 – positive control (β-actin), 22 – negative control. Interpretation of the result: positive results (number of stripe in parenthesis) – 2DL1 (1), 2DL3 (3), 2DL4 (4), 2DL5all (5), 2DL5A (6), 2DL5B (7), 2DS1 (8), 2DS5 (13), 3DL2 (15), 3DL3 (16), 3DS1 (17), 2DP1 (18), 3DP1 (19). 2D – receptor-encoding genes with two extracellular immunoglobulin- like domains, 3D – receptor-encoding genes with three extracellular immunoglobulin-like domains, L – long transmembrane sequence – inhibitory genes, S – short transmembrane sequence – activating genes, P – pseudogene