Clinical and immune features associated with chromosome 13q deletion and PRKCSH downregulation in newly diagnosed multiple myeloma.

BACKGROUND

Newly diagnosed multiple myeloma (NDMM) shows marked immune heterogeneity. Deletion of chromosome 13q [del(13q)] is common in multiple myeloma, yet its immunological significance remains unclear.

METHODS

Peripheral blood immune profiles were evaluated in 132 NDMM patients using flow cytometry and a cytokine bead array. Publicly available transcriptomic cohorts were interrogated using differential gene expression testing, co-expression network analysis (WGCNA), and immune-cell deconvolution to derive del(13q)-related immune signatures, followed by survival analyses.

RESULTS

Compared with 13q-wt cases, del(13q) NDMM exhibited higher peripheral IL-8 and IL-10 levels and increased absolute lymphocyte counts, accompanied by a redistribution of lymphocyte subsets with reduced T-cell representation (including CD4+CD8+ double-positive T cells) and increased NK-cell proportions. Clinically, del(13q) was associated with more advanced disease stage, a higher burden of cytogenetic high-risk lesions, and adverse features such as hypercalcemia, elevated β2-microglobulin, and bone marrow plasmacytosis. Integrative analyses identified PRKCSH as a downregulated hub in del(13q) and linked it to immune-related pathways and infiltration patterns. Lower PRKCSH expression was associated with higher R-ISS stage and worse OS and PFS, and PRKCSH levels correlated positively with CD8+ T cells, resting dendritic cells, and follicular helper T cells while showing inverse associations with naive CD4+ T cells and γδ T cells.

CONCLUSIONS

Del(13q) in NDMM is associated with systemic immune dysregulation and PRKCSH downregulation. Low PRKCSH expression is associated with unfavorable outcomes and may reflect immune pathways and immune cell infiltration.