Genetic evidence against clonotypic B-lymphocytes as reservoir of plasma-cell cancers - PubMed
14 hours ago
- #plasma-cell cancers
- #multiple myeloma
- #B-lymphocytes
- The study investigates whether multiple myeloma (MM) and light-chain amyloidosis (AL) originate from terminally differentiated plasma cells (PC) or earlier clonotypic B cells.
- Single-cell and exome sequencing on highly-purified MM and AL samples was performed to identify the B-cell development stage where driver genetic alterations occur.
- Clonotypic B-cell receptors (BCR) were found in ≤0.4% of B-cell precursors and mature B cells from MM and AL patients, with paired single-cell transcriptomes confirming their immature phenotype.
- Driver genetic alterations were primarily detected in tumor PC and rarely in immature B-cell stages during treatment.
- Clonotypic B cells may sporadically lead to false-positive minimal residual disease assessments when using next-generation sequencing of BCR.
- The findings suggest clonotypic B cells are pre-neoplastic precursors of malignant PC and are unlikely to contribute to disease progression.