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

Alavianmehr, Ali; Mansouri, Marzieh; Ramzi, Mani; Faghih, Marjan; Monabati, Ahmad; Arandi, Nargess; Faghih, Zahra; Farjadian, Shirin

doi:10.1111/iji.12509

Cited by 4 publications

(6 citation statements)

References 39 publications

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“…We did not find any significant differences when looking at presence or absence of KIR genes in patients when compared to the control group. Other studies comparing presence or absence of KIR genes in patients with AML and other hematologic malignancies and controls found differences, but low sample size, heterogeneous groups of leukemia patients, and/or missing p-value correction for multiple testing are limitations of these studies (13)(14)(15)(16)(17).…”

Section: Discussionmentioning

confidence: 92%

“…In recent studies, the presence or absence of certain KIR genes, KIR haplotype motifs, or KIR/KIR-ligand combinations have been reported to be associated with the susceptibility to breast cancer, 8 , 9 colorectal cancer, 10 , 11 or other solid tumors. 12 , 13 Associations of KIR genotypes with the risk of developing AML were investigated in small case-control studies, 14 , 15 , 16 , 17 , 18 and the results were not consistent.…”

Section: Introductionmentioning

confidence: 98%

“…Associations of KIR genotypes with the risk of developing AML were investigated in small casecontrol studies (13)(14)(15)(16)(17) and the results were not consistent.…”

Section: Introductionmentioning

confidence: 99%

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Large case-control study indicates no association of KIR genotype and risk of developing acute myeloid leukemia

et al. 2023

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Immunogenetic association studies may give rise to new hypotheses on the immune surveillance of cancer. We hypothesized that certain combinations of Killer-cell Immunoglobulin-like Receptor (KIR) and HLA genotypes may enhance Natural Killer (NK)-cell immunity against nascent acute myeloid leukemia (AML) and thereby lead to a skewed genotype distribution among patients. For this purpose, we analyzed KIR and HLA genotypes of 1767 German patients with AML and compared the results to data of 51 890 German volunteers who had registered with DKMS. Patient samples were retrieved from the Collaborative Biobank (CoBi) and the Biorepository of the Study Alliance Leukemia (SAL). All samples were genotyped with high-resolution amplicon-based next-generation sequencing. Owing to the large number of controls this study was very sensitive to detect an impact of KIR genotype. Knowledge on KIRs and their cognate HLA ligands allowed for testing of several hypotheses of NK-cell mediated endogenous leukemia surveillance. We did not find significant differences between the two cohorts regarding presence or absence of single KIR genes. When grouped by telomeric or centromeric gene content, the major haplotypes A/A, A/B, and B/B were equally distributed among patients and controls. Using information on KIRs and their HLA ligands, we further tested receptor-ligand models and summation models without revealing markedly significant differences between patients and controls, albeit we observed a trend pointing at a minor protective effect of a low number of inhibitory KIR/KIR-ligand pairs. The results suggest that the KIR/KIR-ligand genotype has no effect on the susceptibility for the development of de novo AML.

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Section: Discussionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 98%

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Large case-control study indicates no association of KIR genotype and risk of developing acute myeloid leukemia

et al. 2023

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“…The protocol of this study was designed based on the Declaration of Helsinki and approved by the SUMS Ethics Committee (IR.SUMS.REC.1400,528). A total of 75 blood samples were collected from newly diagnosed patients with AML from April 2021 to April 2022 and 106 samples were included from our previous study 44 . Due to their low white blood cell counts and low DNA yield, patients undergoing intensive chemotherapy were omitted from the study.…”

Section: Methodsmentioning

confidence: 99%

Association of killer cell immunoglobulin-like receptors and their cognate HLA class I ligands with susceptibility to acute myeloid leukemia in Iranian patients

Mirzazadeh,

Bemani,

Halimi

et al. 2023

Sci Rep

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Acute myeloid leukemia (AML) is one of the most prevalent leukemia in adults. Among the various NK receptors, killer immunoglobulin-like receptors (KIRs) carry out indispensable roles in NK cell development and function through engaging with class I human leukocyte antigens (HLA-I) as their ligands. Besides divergent KIR and HLA loci, KIR/HLA-I combinations have a significant effect on NK cell response. In this case–control study, we aimed to verify the association of KIR/HLA-I combinations with susceptibility to AML in the Southwestern Iranian population. KIR and HLA genotyping was performed with PCR-SSP by some novel primers for 181 patients with AML and 181 healthy controls. According to our results, the frequencies of KIR3DS1 (p = 0.0001, OR = 2.32, 95% CI 1.51–3.58), KIR2DS4fl (p = 0.02, OR = 1.53, 95% CI 1.05–2.21), CxT4 genotypes (p = 0.03, OR = 2.0, 95% CI 1.05–3.82), and T4 gene cluster (p = 0.01, OR = 1.99, 95% CI 1.17–3.41) were significantly higher in patients than controls, while C1/C2 genotype (p = 0.00002, OR = 0.39, 95% CI 0.25–0.61), HLA-A Bw4 (p = 0.02, OR = 0.6, 95% CI 0.38–0.94), and HLA-A*11 (p = 0.03, OR = 0.57, 95% CI 0.34–0.95) alleles were more frequent in controls. In addition, inhibitory (i)KIR/HLA-I combinations analysis revealed higher frequencies of KIR2DL1( +)/HLA-C2( +), KIR2DL2/3( +)/HLA-C1( +), KIR3DL1( +)/HLA-A Bw4( +), and KIR3DL2( +)/HLA-A*03/11( +) in the control group (p = 0.002, OR = 0.49, 95% CI 0.3–0.78; p = 0.04, OR = 0.62, 95% CI 0.39–0.99; p = 0.04, OR = 0.63, 95% CI 0.4–0.99; and p = 0.03, OR = 0.62, 95% CI 0.4–0.95, respectively). Overall, the number of iKIR/HLA-I combinations was more in the control group. Moreover, KIR3DS1( +)/HLA-B Bw4Ile80( +) and the sum of HLA-B Bw4/A Bw4 combined with KIR3DS1 as activating KIR/HLA-I combinations were more frequent among patients than controls (p = 0.01, OR = 1.99, 95% CI 1.14–3.49 and p = 0.005, OR = 1.97, 95% CI 1.22–3.19, respectively). In conclusion, our results postulate that inhibitory combinations play a protective role against AML by developing potent NK cells during education. It is noteworthy that KIR/HLA-I combination studies can be applicable in donor selection for allogeneic NK cell therapy in hematological malignancies.

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“…While AML patients ( n = 169) exhibit high expression of KIR activating receptors, especially KIR3DS1, normal subjects ( n = 167) express KIR inhibitory receptors, especially KIR2DL1 and KIR3DL1. It has been proposed that the increased expression of KIR-activating receptors in patients probably leads to the hyperactivation of these cells following the encounter with leukemic cells and further the exhaustion of NK cells and the progression of cancer [ 64 ]. Interestingly, some fungal infections, such as A. fumigatus, promote NK cell exhaustion in AML patients leading to their reduced cytotoxic function against leukemic cells.…”

Section: Exhausted Nk Cells and Leukemiamentioning

confidence: 99%

The role of exhausted natural killer cells in the immunopathogenesis and treatment of leukemia

Barshidi,

Ardeshiri,

Ebrahimi

et al. 2024

Cell Commun Signal

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The immune responses to cancer cells involve both innate and acquired immune cells. In the meantime, the most attention has been drawn to the adaptive immune cells, especially T cells, while, it is now well known that the innate immune cells, especially natural killer (NK) cells, play a vital role in defending against malignancies. While the immune cells are trying to eliminate malignant cells, cancer cells try to prevent the function of these cells and suppress immune responses. The suppression of NK cells in various cancers can lead to the induction of an exhausted phenotype in NK cells, which will impair their function. Recent studies have shown that the occurrence of this phenotype in various types of leukemic malignancies can affect the prognosis of the disease, and targeting these cells may be considered a new immunotherapy method in the treatment of leukemia. Therefore, a detailed study of exhausted NK cells in leukemic diseases can help both to understand the mechanisms of leukemia progression and to design new treatment methods by creating a deeper understanding of these cells. Here, we will comprehensively review the immunobiology of exhausted NK cells and their role in various leukemic malignancies.

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

Cited by 4 publications

References 39 publications

Large case-control study indicates no association of KIR genotype and risk of developing acute myeloid leukemia

Large case-control study indicates no association of KIR genotype and risk of developing acute myeloid leukemia

Association of killer cell immunoglobulin-like receptors and their cognate HLA class I ligands with susceptibility to acute myeloid leukemia in Iranian patients

The role of exhausted natural killer cells in the immunopathogenesis and treatment of leukemia

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