@Article{biocell.2025.063960,
AUTHOR = {Natalia Lehman, Agnieszka Bojarska-Junak, Michał Zarobkiewicz},
TITLE = {Butyrophilin Downregulation in Chronic Lymphocytic Leukaemia: An Important Barrier to <b>γδ</b> T Cell-Mediated Cytotoxicity},
JOURNAL = {BIOCELL},
VOLUME = {49},
YEAR = {2025},
NUMBER = {6},
PAGES = {1085--1099},
URL = {http://www.techscience.com/biocell/v49n6/62466},
ISSN = {1667-5746},
ABSTRACT = { <b>Introduction:</b> Butyrophilins (BTNs) belong to the immunoglobulin superfamily; they play crucial roles in immune regulation, especially in γδ T cell activation. While their expression has been studied in solid tumours, their involvement in hematologic malignancies remains poorly understood. <b>Objectives:</b> We hypothesised that BTNs are dysregulated in chronic lymphocytic leukaemia (CLL), contributing to γδ T cell dysfunction and potentially influencing disease progression. <b>Methods:</b> In this study, we analyzed publicly available microarray and RNA-seq datasets to investigate the expression patterns of <i>BTN</i> genes in CLL. <b>Results:</b> Our findings reveal significant dysregulation of <i>BTN</i> gene expression in CLL, with <i>BTN2A1</i>, <i>BTN3A1</i>, <i>BTN3A2</i>, and <i>BTN3A3</i> being markedly downregulated in peripheral blood mononuclear cells (PBMCs) and bone marrow samples from CLL patients compared to healthy volunteers, while <i>BTN1A1</i> was upregulated. Furthermore, <i>BTN2A2</i> was selectively downregulated in neoplastic B cells, whereas <i>BTN3A1</i> was upregulated in T cells from CLL patients compared to healthy volunteers. Notably, lower <i>BTN</i> expression was associated with an unmutated <i>IGVH</i> status and male sex. Kaplan-Meier survival analysis demonstrated that higher expression of <i>BTN2A1</i>, <i>BTN3A1</i>, <i>BTN3A2</i>, and <i>BTN3A3</i> correlated with a significantly longer overall survival. <b>Conclusions:</b> Given the established role of BTN2A1 and BTN3A1 in the phosphoantigen-mediated activation of Vδ2 γδ T cells, their downregulation may contribute to γδ T cell dysfunction in CLL. These results highlight the potential prognostic value of <i>BTN</i> gene expression in CLL and underscore the need for further studies exploring its mechanistic role in disease progression and immune evasion.},
DOI = {10.32604/biocell.2025.063960}
}