Researchers of a study developed a transcriptomic atlas mapping normal plasma cell development, elucidating the distinct biological trajectories of light-chain amyloidosis (AL) and multiple myeloma (MM) cells. The findings show AL plasma cells resemble those from secondary lymphoid organs, while MM cells align more with peripheral blood and newborn bone marrow plasma cells. This variation explains their different clinical impacts—AL leads to organ-impacting amyloid fibrils independently of tumor burden, whereas MM causes significant bone marrow proliferation and associated complications like anemia and bone damage.

Additionally, leveraging cutting-edge single-cell RNA sequencing, the study examines the heterogeneity and transcriptional programs (TPs) of tumor plasma cells in both diseases, identifying specific TPs linked to their origins and behaviors. Notably, variations in gene expression related to protein glycosylation and ribosome biogenesis provide insights into the distinct pathologies of AL and MM, despite some genetic overlaps. These findings reveal complex interactions between a tumor’s genetic profile and its microenvironment.

Reference: Corre J. Why is amyloidosis not multiple myeloma? Blood. Updated October 28, 2021. Accessed May 13, 2024. https://ashpublications.org/blood/article/138/17/1514/477397/Why-is-amyloidosis-not-multiple-myeloma