Certain Killer immunoglobulin like receptor (KIR)/ KIR HLA class I ligand genotypes influence NK antitumor activity in acute myelogenous leukemia but not in acute lymphoblastic leukemia. A case control leukemia association study

Viktoria Plamenova Varbanova,Anastasiya Petrova Mihaylova,Elissaveta Naumova,Snejina Mihailova

doi:10.4274/tjh.galenos.2019.2019.0079

Viktoria Plamenova Varbanova, Anastasiya Petrova Mihaylova + Show 2 more

Open Access

https://doi.org/10.4274/tjh.galenos.2019.2019.0079

Copy DOI

Abstract

Objective:Natural killers (NK) cell function is mainly controlled by the expression of killer immunoglobulin-like receptors (KIRs) and their ligation with the corresponding ligands. The objective of this study was to investigate the putative association of KIRs, HLA class I ligands, and KIR/ligand combinations with rates of development of acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), and chronic myeloid leukemia (CML).Materials and Methods:The KIR/HLA I genotypes of 82 patients with leukemia (ALL, n=52; AML, n=17; and CML, n=13) were determined by PCR-SSP method and compared with genotypes of healthy controls (n=126).Results:KIR genotype frequency differed significantly between myelogenous leukemia patients and healthy controls for KIR2DL5A (17.6% vs. 47.7%, p=0.02), KIR3DS1 (17.6% vs. 47.6%, p=0.02), and KIR2DS4*001 (36.6% vs. 20.2%, p=0.017). The incidence of homozygous HLA-BBw4 (31.0% vs. 12.5%, p=0.042) and HLA-Bw4Thr80 Thr80 (13.0% vs. 1.2%, p=0.01) was significantly elevated in myeloid leukemia patients compared to healthy controls. KIR/HLA class I ligand profile KIR3DS1(+)/L (-) was decreased and KIR3DL2(+)/HLA-A3/11(-) was increased among myeloid leukemia cases compared to controls.Conclusion:These data suggest that the activity of NK cells as determined by inherited KIR/HLA class I ligand polymorphisms influences the susceptibility to myelogenous leukemia, but not to lymphoblastic leukemia. Additionally, the KIR genotype characterized by the absence of the inhibitory KIR2DL2 and the activating KIR2DS2 and KIR2DS3 (ID2) was found at a lower frequency in patients compared to controls, which confirmed the need for complex analysis based on all possible KIR/HLA class I ligand polymorphism combinations.

Highlights

In 2015, 4062 patients with leukemia were treated and/or monitored in the Republic of Bulgaria [1]
These data suggest that the activity of Natural killers (NK) cells as determined by inherited killer immunoglobulin-like receptors (KIRs)/HLA class I ligand polymorphisms influences the susceptibility to myelogenous leukemia, but not to lymphoblastic leukemia
The KIR genotype characterized by the absence of the inhibitory KIR2DL2 and the activating KIR2DS2 and KIR2DS3 (ID2) was found at a lower frequency in patients compared

Summary

Introduction

In 2015, 4062 patients with leukemia were treated and/or monitored in the Republic of Bulgaria [1]. NK cells play an important role in antitumor immune defense [2,3] Their function is controlled by the interaction of cell surface receptors with appropriate ligands, among which the most important and best studied are killer immunoglobulin-like receptors (KIRs) and their HLA class I ligands [4,5,6,7,8]. HLA C molecules with amino acid residues Ser and Asn at positions 70 and 80, respectively (Ser and Asn80), form the HLA-C1 KIR ligand group, which binds KIR2DL1 and KIR2DS2. HLA-B class I molecules with the Bw4 epitope are ligands for KIR3DL1 and KIR3DS1 [7,8,14,15]. KIR3DL2 recognizes HLA-A3 and HLA-A11 specific to certain peptides such as Epstein-Barr virus peptides [16,17]

Methods

Results

Discussion

Conclusion