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

Varbanova, V.; Mihailova, Snezhina; Naumova, Elissaveta; Mihaylova, Anastasiya

doi:10.4274/tjh.galenos.2019.2019.0079

Cited by 10 publications

(13 citation statements)

References 36 publications

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“…Shahsavar et al reported a non‐significant increase in the frequency of the KIR3DS1 gene and a significantly reduced frequency of the KIR2DS3 gene in patients with AML compared to controls at Shariati Hospital, Tehran, Iran—a referral centre that admits patients from all over the country (Shahsavar et al., 2010). In contrast to our results, a lower frequency of KIR3DS1 was previously reported in Bulgarian patients with AML by Varbanova et al (Varbanova et al., 2019). In data reported by Vejbaesya et al, no significant difference in KIR gene distribution was found between Thai patients with AML and controls (Vejbaesya, Sae‐Tam, Khuhapinant, & Srinak, 2014).…”

Section: Discussioncontrasting

confidence: 99%

“…There are just a few studies about the association of KIR genes with AML as Shahsavar et al reported negative associations between KIR2DS3 and KIR3DS1 with AML in Iranian patients (Shahsavar et al., 2010) and Varbanova et al found negative association of KIR2DL5a and positive association of KIR2DS4fl with AML in Bulgarians (Varbanova, Mihailova, Naumova, & Mihaylova, 2019).…”

Section: Introductionmentioning

confidence: 99%

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Association of killer‐cell immunoglobulin‐like receptor genes with acute myelogenous leukaemia

Alavianmehr

Mansouri

Ramzi

et al. 2020

Int J Immunogenetics

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Killer‐cell immunoglobulin‐like receptors (KIRs) are important because of their key roles in NK cell development and function. Some KIR genes have been associated with the incidence of haematological malignancies. This study was designed to determine whether the inheritance of specific KIR genes is associated with susceptibility to acute myelogenous leukaemia (AML) in Persians living in south‐western Iran. KIR genes and KIR2DS4 variants were typed by polymerase chain reaction–sequence‐specific primer (PCR‐SSP) in 167 patients with AML and 169 healthy controls. Our results showed 10% of patients—mostly females—were classified as M3. Flt3 mutations were detected in 26% of patients, most of whom had internal tandem duplication (ITD). The frequency of activating KIRs (aKIRs)—mainly KIR3DS1—was higher in patients, whereas inhibitory KIRs (iKIRs)—particularly KIR3DL1 and KIR2DL1—were more common among controls. The incidence of the KIR2DS4fl allele was higher among patients with non‐M3 AML than controls. We also found a higher frequency of 4 or more iKIR genes in the controls and a higher frequency of 4 or more aKIR genes in the patients. Individuals with more iKIR than aKIR belonged predominantly to the control group. Individuals with the telomeric AA genotype who had inherited the KIR2DS4fl allele were more frequent in the patient group. According to our results, increased frequency of aKIRs in patients with AML may lead to the hyperactivation of NK cells against malignant cells with reduced or lack of HLA class I molecules followed by NK cell exhaustion which allow malignant cells to progress.

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Section: Discussioncontrasting

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Association of killer‐cell immunoglobulin‐like receptor genes with acute myelogenous leukaemia

Alavianmehr

Mansouri

Ramzi

et al. 2020

Int J Immunogenetics

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“…The role of KIR2DL5 gene and its allelic variants for NK activity regulation is supported by the finding of other researchers as Shah-Hosseini et al 16 who demonstrated a higher frequency of KIR2DL5A allele in HBV recovered individuals compared to controls. The higher distribution of inhibitory KIR3DL1*004 observed by us in chronic HBV carriers may suggest increased NK-cell inhibition in chronic disease, although some data demonstrate lack of expression of the encoded receptor 28 .…”

Section: Discussionmentioning

confidence: 74%

KIR/HLA ligands immunogenetics markers associated with outcome of hepatitis B virus infection in the Bulgarian population

Varbanova¹,

Popov²,

Grigorova³

et al. 2021

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

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Background. Hepatitis B virus (HBV) infection is one of the most common infections worldwide, having negative impact on world health due to the tendency for chronification with late complications such as liver cirrhosis and hepatocellular carcinoma. Natural killer (NK) cells as part of innate antiviral defense influence the clinical course of HBV infection: elimination of the virus or chronic disease. Aim. Therefore, we investigated the polymorphisms of the main gene systems, regulating NK-cell function: killer cell immunoglobulin-like receptors (KIRs) and their appropriate HLA class I ligands in 144 HBV infected patients (124 chronic carriers and 20 spontaneously recoved) and 126 ethnically matched healthy controls from the Bulgarian population in a case-control study. Methods. KIRs and HLA ligands were determined by PCR-SSP or PCR high-resolution typing methods. Results. KIR2DL5B allele variant was significantly less frequent in spontaneously recovered (SR) patients compared to healthy controls (10.0% vs. 45.5%, P corr =0.006). The presence of KIR3DL1*004 allele was higher in chronic HBV carriers (CH) than in controls (33.1% vs. 17.6%, P corr =0.036). Additionally, SR patients differed from healthy individuals by the lower frequency of HLA-Bw4 Ile80 group ligands (30.0% vs 63.7%, P=0.015). Three KIR genotypes were found more frequent in healthy in comparison with HBV infected individuals: ID2 (13.5% vs 5.6%, P=0.025), KIR genotype containing 6 activating KIRs (18.0% vs 7.6%, P=0.017), and KIR genotype composed of 4 activating and 5 inhibitory KIRs (23.8% vs 5.6%, P=0.001). Conclusion. These data suggest that inherited KIR and HLA class I ligand polymorphisms may influence the clinical course of HBV infection.

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“…Various recent reports suggest a potential role for KIR receptors in the development of CML and response to TKI treatment, although the studies included relatively small number of samples and reported contrasting findings 36–39 …”

Section: Discussionmentioning

confidence: 99%

“…35 Various recent reports suggest a potential role for KIR receptors in the development of CML and response to TKI treatment, although the studies included relatively small number of samples and reported contrasting findings. [36][37][38][39] We recruited 190 patients with chronic-phase CML treated with TKIs and KIR genes, the KLRK1 SNP (rs1049174), and KIR ligand genes HLA-A, HLA-B, HLA-C, HLA-G, HLA-F, MICA, and MICB were genotyped to characterize the effects on MR of NK receptors and their respective ligands in this population. Apart from assessing KIR gene variability, we were interested in learning more about the network of NK receptors and ligands that characterize the action of NK cells.…”

Section: Discussionmentioning

confidence: 99%

Natural killer cell receptors and ligand variants modulate response to tyrosine kinase inhibitors in patients with chronic myeloid leukemia

Closa

Xicoy

Zamora

et al. 2022

HLA

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Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm treated with tyrosine kinase inhibitors (TKIs). Although survival rates have improved, response to these treatments is highly heterogeneous. Variations in response rates may be due to different causes such as, treatment adherence, mutations in the BCR‐ABL1 gene, clonal evolution and amplification of the BCR‐ABL1 gene, but innate immune response is also considered to play a very important role and, specifically, NK cell activity through their receptors and ligands, could be determinant. The aim of this retrospective study was to explore the role of different activating and inhibiting KIR genes as well as the activating NKG2D receptor, present in NK cells, and also their respective ligands, HLA‐A, ‐B, ‐C, ‐G, ‐F, MICA and MICB, in the progression of 190 patients with CML and treated at two hospitals from Barcelona between 2000 and 2019. Early molecular response (EMR), major molecular response (MMR) or MR3.0 and deep molecular response (DMR) or MR4.0 were correlated. As control samples, healthy donors from the Barcelona Blood Bank were analyzed. The presence of KIR2DL2/KIR2DS2 was associated with the achievement of EMR, MR3.0, and MR4.0. Carriers of the higher expression NKG2D variant and MICA*009:01 were also likely to achieve molecular response (MR). The most remarkable difference between CML patients and controls was a higher frequency of the lower expression NKG2D variant in CML patients. In summary, our results showed that activating NK receptor phenotypes might help to achieve MR and DMR in CML patients treated with TKIs although confirmatory studies are necessary.

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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

Cited by 10 publications

References 36 publications

Association of killer‐cell immunoglobulin‐like receptor genes with acute myelogenous leukaemia

Association of killer‐cell immunoglobulin‐like receptor genes with acute myelogenous leukaemia

KIR/HLA ligands immunogenetics markers associated with outcome of hepatitis B virus infection in the Bulgarian population

Natural killer cell receptors and ligand variants modulate response to tyrosine kinase inhibitors in patients with chronic myeloid leukemia

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