Role of Polymorphisms of NKG2D Receptor and Its Ligands in Acute Myeloid Leukemia and Human Stem Cell Transplantation

Journal article

Machuldova, A., Holubova, M., Caputo, V.S., Cedikova, M., Jindra, P., Houdova, L. and Pitule, P. (2021). Role of Polymorphisms of NKG2D Receptor and Its Ligands in Acute Myeloid Leukemia and Human Stem Cell Transplantation. Frontiers in Immunology. 12, p. 651751. https://doi.org/10.3389/fimmu.2021.651751
AuthorsMachuldova, A., Holubova, M., Caputo, V.S., Cedikova, M., Jindra, P., Houdova, L. and Pitule, P.
AbstractNatural killer cells possess key regulatory function in various malignant diseases, including acute myeloid leukemia. NK cell activity is driven by signals received through ligands binding activating or inhibitory receptors. Their activity towards elimination of transformed or virally infected cells can be mediated through MICA, MICB and ULBP ligands binding the activating receptor NKG2D. Given the efficiency of NK cells, potential target cells developed multiple protecting mechanisms to overcome NK cells killing on various levels of biogenesis of NKG2D ligands. Targeted cells can degrade ligand transcripts via microRNAs or modify them at protein level to prevent their presence at cell surface via shedding, with added benefit of shed ligands to desensitize NKG2D receptor and avert the threat of destruction via NK cells. NK cells and their activity are also indispensable during hematopoietic stem cell transplantation, crucial treatment option for patients with malignant disease, including acute myeloid leukemia. Function of both NKG2D and its ligands is strongly affected by polymorphisms and particular allelic variants, as different alleles can play variable roles in ligand-receptor interaction, influencing NK cell function and HSCT outcome differently. For example, role of amino acid exchange at position 129 in MICA or at position 98 in MICB, as well as the role of other polymorphisms leading to different shedding of ligands, was described. Finally, match or mismatch between patient and donor in NKG2D ligands affect HSCT outcome. Having the information beyond standard HLA typing prior HSCT could be instrumental to find the best donor for the patient and to optimize effects of treatment by more precise patient-donor match. Here, we review recent research on the NKG2D/NKG2D ligand biology, their regulation, description of their polymorphisms across the populations of patients with AML and the influence of particular polymorphisms on HSCT outcome.
KeywordsImmunology; natural killer group 2 member D; MICA; MICB; ULBP; hematopoietic stem cell transplant; acute myeloid leukemia; polymorphism
Year2021
JournalFrontiers in Immunology
Journal citation12, p. 651751
PublisherFrontiers Media
ISSN1664-3224
Digital Object Identifier (DOI)https://doi.org/10.3389/fimmu.2021.651751
Publication dates
Online30 Mar 2021
Publication process dates
Accepted15 Mar 2021
Deposited13 Apr 2021
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Open
Licensehttp://creativecommons.org/licenses/by/4.0/
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