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. 2019 Nov 18;36(4):238-246.
doi: 10.4274/tjh.galenos.2019.2019.0079. Epub 2019 Jul 24.

Certain Killer Immunoglobulin-Like Receptor (KIR)/KIR HLA Class I Ligand Genotypes Influence Natural Killer Antitumor Activity in Myelogenous Leukemia but Not in Acute Lymphoblastic Leukemia: A Case Control Leukemia Association Study

Viktoria Plamenova Varbanova  1 , Snejina Mihailova  2 , Elissaveta Naumova  2 , Anastasiya Petrova Mihaylova  2
Affiliations

Certain Killer Immunoglobulin-Like Receptor (KIR)/KIR HLA Class I Ligand Genotypes Influence Natural Killer Antitumor Activity in Myelogenous Leukemia but Not in Acute Lymphoblastic Leukemia: A Case Control Leukemia Association Study

Viktoria Plamenova Varbanova et al. Turk J Haematol. .

Abstract
in English, Turkish

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.

Amaç: Doğal öldürücü (NK) hücre fonksiyonu temel olarak öldürücü immünoglobulin-benzeri reseptör (KIR) yüzey ifadesi ve bunların ilgili liganda bağlanması ile ilişkilidir. Bu çalışmanın amacı KIR, HLA sınıf I ligandlar ve KIR/ligand ilişkisinin akut lenfoblastik lösemi (ALL), akut myeloid lösemi (AML) ve kronik myeloid lösemi (KML) oluşumu ile ilişkisini araştırmaktır.

Gereç ve yöntemler: Seksen iki lösemi hastasının (ALL, n=52; AML, n=17; ve KML, n=13) KIR/HLA I genotipleri PCR-SSP metodu ile çalışıldı ve sağlıklı kontrollerin (n=126) genotipleri ile karşılaştırıldı.

Bulgular: KIR genotip frekansı myeloid lösemi hastaları ve sağlıklı kontroller arasında KIR2DL5A (%17,6 vs. %47,7, p=0,02), KIR3DS1 (%17,6 vs. %47,6, p=0,02), ve KIR2DS4*001 (%36,6 vs. %20,2, p=0,017) açısından belirgin farklılık gösterdi. Homozigot HLA-BBw4 (%31,0 vs. %12,5, p=0,042) ve HLA-Bw4Thr80 Thr80 (%13,0 vs. %1,2, p=0,01) sıklığı da myeloid lösemi hastalarında sağlıklı kontrollere göre belirgin olarak daha yüksekti. Kontrollerle karşılaştırıldığında myeloid lösemi hastalarında KIR/HLA sınıf I ligand profili olarak KIR3DS1(+)/L(-) azalmış ve KIR3DL2(+)/HLA-A3/11(-) artmış olarak bulundu.

Sonuç: Bu bulgular, kalıtılan KIR/HLA sınıf I ligand polimorfizmleri ile belirlenen NK hücre aktivitesinin myeloid lösemiye yatkınlığı etkilediği ancak lenfoid lösemi yatkınlığını etkilemediğini düşündürmektedir. Ayrıca inhibitor KIR2DL2, aktivatör KIR2DS2 ve KIR2DS3 (ID2) ile karakterize KIR genotipi, hastalarda kontrollere oranla daha düşük bulundu, bu da bütün olası KIR/HLA sınıf I ligand polimorfizmlerine dayanan kompleks analizlerin gerekliliğini desteklemektedir.

Keywords: Chronic myeloid leukemia; Acute lymphoblastic leukemia; Acute myeloblastic leukemia.

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Conflict of interest statement

Conflict of Interest: The authors of this paper have no conflicts of interest, including specific financial interests, relationships, and/or affiliations relevant to the subject matter or materials included.

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