TSPAN32, a member of the tetraspanin superfamily, is located in the imprinted gene domain of chromosome 11p15.5, a critical tumor-suppressor gene region. It is highly expressed in immune cells like NK cells and CD8+ T cells and seems to be involved in regulating immune cell activation and metabolic adaptations, with potential roles in hematopoiesis [5].

In chronic myeloid leukemia (CML), TSPAN32 expression is repressed by BCR-ABL. Ectopic TSPAN32 expression inhibits the proliferation of Ph+ cell lines and BCR-ABL induced leukemia progression in murine models, impairs leukemia stem cell proliferation. Mechanistically, it interacts with PTEN, increases its protein level, and reduces PI3K-AKT signaling activity [1]. In autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and multiple sclerosis (MS), TSPAN32 is downregulated. In SLE, B cell activation and IFN-α are associated with TSPAN32 downregulation; in RA, it is downregulated in pathogenic T-cell populations and its overexpression inhibits pro-inflammatory cytokine production; in MS, it is downregulated in memory T cells [2,3,4].

In conclusion, TSPAN32 plays a crucial role in regulating immune cell physiology and responses. Findings from in vivo studies, especially in mouse models, have revealed its significance in CML pathogenesis and autoimmune diseases, highlighting its potential as a diagnostic marker, prognostic indicator, and therapeutic target in these disease areas.

References:

1. Qiu, Qiang, Sun, Yuanyuan, Yang, Linyu, Li, Zhihui, Hu, Yiguo. 2023. TSPAN32 suppresses chronic myeloid leukemia pathogenesis and progression by stabilizing PTEN. In Signal transduction and targeted therapy, 8, 90. doi:10.1038/s41392-022-01290-7. https://pubmed.ncbi.nlm.nih.gov/36854750/

2. Fagone, Paolo, Mangano, Katia, Di Marco, Roberto, Muñoz-Valle, José Francisco, Nicoletti, Ferdinando. 2021. Altered Expression of TSPAN32 during B Cell Activation and Systemic Lupus Erythematosus. In Genes, 12, . doi:10.3390/genes12060931. https://pubmed.ncbi.nlm.nih.gov/34207245/

3. Mangano, Katia, Munoz-Valle, Jose' Francisco, Palafox-Sánchez, Claudia Azucena, Fagone, Paolo, Nicoletti, Ferdinando. 2024. Tetraspanin32 (TSPAN32) is downregulated in rheumatoid arthritis: Evidence from animal models and patients. In Scandinavian journal of immunology, 100, e13410. doi:10.1111/sji.13410. https://pubmed.ncbi.nlm.nih.gov/39333050/

4. Basile, Maria Sofia, Mazzon, Emanuela, Mangano, Katia, Fagone, Paolo, Cavalli, Eugenio. 2020. Impaired Expression of Tetraspanin 32 (TSPAN32) in Memory T Cells of Patients with Multiple Sclerosis. In Brain sciences, 10, . doi:10.3390/brainsci10010052. https://pubmed.ncbi.nlm.nih.gov/31963428/

5. Scuderi, Grazia, Mangano, Katia, Petralia, Maria Cristina, Fagone, Paolo, Nicoletti, Ferdinando. 2025. Comprehensive Analysis of TSPAN32 Regulatory Networks and Their Role in Immune Cell Biology. In Biomolecules, 15, . doi:10.3390/biom15010107. https://pubmed.ncbi.nlm.nih.gov/39858501/