Unveiling the link between genetic alterations in gamma secretase and BCMA surface density in multiple myeloma.

ABSTRACT

Cattaneo et al. report a unique case of a multiple myeloma patient with elevated B-cell maturation antigen (BCMA) surface density, potentially due to genetic alterations in the gamma-secretase protease complex-responsible for BCMA cleavage from plasma cells. No mutations in the BCMA gene were detected, but there was partial deletion of PSEN1 and amplification of PSEN2 (components of the gamma-secretase complex), which may explain the lack of response to the gamma-secretase inhibitor DAPT. This case, along with recent published literature, underscores the significance of gamma secretase in modulating BCMA density and the potential impact of its genetic alterations. Commentary on Cattaneo et al. Genetic defects of gamma-secretase genes in a multiple myeloma patient with high and dysregulated BCMA surface density A case report. Br J Haematol 2024;204571-575.