Related Experiment Video
Updated: Jun 16, 2026

A Novel Feeder-free System for Mass Production of Murine Natural Killer Cells In Vitro
Published on: January 9, 2018
BAP1 loss impairs IFN-γ signaling and enhances NK cell-mediated cytotoxicity in myeloid leukemia
Chiara Badami1,2, Erna Islamagic1,2, Linnea Blomén1,2
1TIMM Laboratory at Sahlgrenska Center for Cancer Research, University of Gothenburg, Box 450, 405 30, Gothenburg, Sweden.
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.
Related Concept Videos
The Intrinsic Apoptotic Pathway
NF-κB-dependent Signaling Pathway
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
Cells of the Innate Immune Response
Phagocytes
Phagocytes police the peripheral tissues by removing cellular debris and responding to the invasion of foreign substances or pathogens. Many phagocytes attack and remove microorganisms even before lymphocytes detect them. The human body has two general...
Cytotoxic T Cells-mediated Immune Response
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
The Extrinsic Apoptotic Pathway

