Randomized trial demonstrates the role of CYLD in regulating RelB activity and MM cell behavior, implying potential therapeutic avenues.
Key Points
This research aims to elucidate the role of CYLD in the non-canonical RelB NF-κB transcription axis and its implications in multiple myeloma pathogenesis.
Isolated primary CD138+ plasma cells from bone marrow of 74 patients with multiple myeloma using MACS separation.
Conducted NF-κB DNA binding assays and quantitative RT-PCR on patient-derived myeloma cell lines.
Generated CYLD deficient cell lines using CRISPR-Cas9 for biochemical studies.
Increased nuclear RelB activity correlated with high RelB expression in newly diagnosed multiple myeloma patients.
CYLD deficient MMCLs exhibited higher canonical NF-κB activity compared to CYLD sufficient lines (KP-6 vs JIM3).
Absence of CYLD led to higher levels of pro-survival factors and chemokine receptors promoting cell survival and migration.