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

Heidenreich F, Falk B, Baldauf H, Massalski C, Schäfer G, Rücker-Braun E, Altmann H, Sauter J, Solloch UV, Lange V, Stölzel F, Röllig C, Middeke JM, von Bonin M, Thiede C, Schäfer-Eckart K, Müller-Tidow C, Krause S, Kraus S, Kaufmann M, Hänel M, Serve H, Neubauer A, Bornhäuser M, Schmidt AH, Schetelig J (2023)

Publication Type: Journal article

Publication year: 2023

Journal

Blood Advances American Society of Hematology

Book Volume: 7

Pages Range: 2994-3004

Journal Issue: 13

DOI: 10.1182/bloodadvances.2022008514

Abstract

Immunogenetic association studies may give rise to new hypotheses on the immune surveillance of cancer. We hypothesized that certain combinations of killer 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 with that of the data of 51 890 German volunteers who had registered with German bone marrow donor file (DKMS). Patient samples were retrieved from the Collaborative Biobank and the biorepository of the Study Alliance Leukemia. All samples were genotyped with high-resolution amplicon-based next-generation sequencing. Because of the large number of controls, this study was very sensitive to detect the 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 2 cohorts in regard to the presence or absence of single KIR genes. When grouped based on telomeric or centromeric gene content, the major haplotypes A/A, A/B, and B/B were equally distributed among patients and control subjects. 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.

Authors with CRIS profile

Stefan Krause Department of Medicine 5 – Haematology and Oncology

Involved external institutions

DKMS Life Science Lab gGmbH DE Germany (DE) Universitätsklinikum Carl Gustav Carus Dresden DE Germany (DE) DKMS Deutsche Knochenmarkspenderdatei DE Germany (DE) Klinikum Nürnberg DE Germany (DE) Universitätsklinikum Heidelberg DE Germany (DE) Universitätsklinikum Würzburg DE Germany (DE) Robert-Bosch-Krankenhaus DE Germany (DE) Klinikum Chemnitz DE Germany (DE) Universitätsklinikum Frankfurt am Main (KGU) DE Germany (DE) Philipps-Universität Marburg DE Germany (DE)

How to cite

APA:

Heidenreich, F., Falk, B., Baldauf, H., Massalski, C., Schäfer, G., Rücker-Braun, E.,... Schetelig, J. (2023). Large case-control study indicates no association of KIR genotype and risk of developing acute myeloid leukemia. Blood Advances, 7(13), 2994-3004. https://doi.org/10.1182/bloodadvances.2022008514

MLA:

Heidenreich, Falk, et al. "Large case-control study indicates no association of KIR genotype and risk of developing acute myeloid leukemia." Blood Advances 7.13 (2023): 2994-3004.

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