Authors
Chiara Badami, Erna Islamagic, Linnea Blomén, Frida Svensson, Theebiga Kathirkamanathan, Kristoffer Hellstrand, Elin Bernson, Fredrik B Thorén
Published in
Cancer immunology, immunotherapy : CII. Volume 75. Issue 6. Jun 15, 2026. Epub Jun 15, 2026.
Abstract
Natural killer (NK) cells recognize and eliminate malignant cells through multiple receptor-ligand interactions. To uncover genetic determinants of the susceptibility of myeloid leukemia cells to NK cell cytotoxicity, we analyzed several genome-wide CRISPR screens. Among recurrent hits, the BRCA1-associated protein 1 (BAP1) gene emerged as a key factor protecting K562 leukemic cells from NK cell-mediated killing. Using BAP1 knockout (KO) models, we found that loss of BAP1 alone did not alter NK cell sensitivity. However, upon interferon-γ (IFN-γ) stimulation, BAP1 KO K562 cells exhibited reduced HLA class I induction, triggered enhanced NK cell degranulation, and showed increased sensitivity to NK cell-mediated cytotoxicity compared with wild-type cells. Further experiments revealed that BAP1-deficient cells displayed reduced expression of the IFN-γ receptor 1 (IFN-γ-R1). BAP1 knockdown across multiple myeloid leukemia cell lines selectively decreased HLA-E and IFN-γ-R1 expression in ASXL1-mutant backgrounds. These findings suggest that BAP1 may contribute to the regulation of IFN-γ responsiveness and immune evasion in myeloid leukemia.
PMID:
42295372
Bibliographic data and abstract were imported from PubMed on 15 Jun 2026.
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