Characterization of BCMA Expression in Circulating Rare Single Cells of Patients with Plasma Cell Neoplasms

Authors

Libere J Ndacayisaba
Kate E Rappard
Stephanie N Shishido
Sonia M Setayesh
Guilin Tang
Pei Lin
Nicholas Matsumoto
Ching-Ju Hsu
Rafael Nevarez
Carmen Ruiz Velasco
Amin Naghdloo
Eric Yang
Kevin Kelly
James Hicks
Jeremy Mason
Robert Z Orlowski
Elisabet E Manasanch
Peter Kuhn

Publication Date

11-3-2022

Journal

International Journal of Molecular Sciences

Abstract

B-cell maturation antigen (BCMA), a key regulator of B-cell proliferation and survival, is highly expressed in almost all cases of plasma cell neoplasms and B-lymphoproliferative malignancies. BCMA is a robust biomarker of plasma cells and a therapeutic target with substantial clinical significance. However, the expression of BCMA in circulating tumor cells of patients with hematological malignancies has not been validated for the detection of circulating plasma and B cells. The application of BCMA as a biomarker in single-cell detection and profiling of circulating tumor cells in patients' blood could enable early disease profiling and therapy response monitoring. Here, we report the development and validation of a slide-based immunofluorescence assay (i.e., CD138, BCMA, CD45, DAPI) for enrichment-free detection, quantification, and morphogenomic characterization of BCMA-expressing cells in patients (N = 9) with plasma cell neoplasms. Varying morphological subtypes of circulating BCMA-expressing cells were detected across the CD138(+/-) and CD45(+/-) compartments, representing candidate clonotypic post-germinal center B cells, plasmablasts, and both normal and malignant plasma cells. Genomic analysis by single-cell sequencing and correlation to clinical FISH cytogenetics provides validation, with data showing that patients across the different neoplastic states carry both normal and altered BCMA-expressing cells. Furthermore, altered cells harbor cytogenetic events detected by clinical FISH. The reported enrichment-free liquid biopsy approach has potential applications as a single-cell methodology for the early detection of BCMA+ B-lymphoid malignancies and in monitoring therapy response for patients undergoing anti-BCMA treatments.

Keywords

Humans, B-Cell Maturation Antigen, Neoplastic Cells, Circulating, Multiple Myeloma, Plasmacytoma, Plasma Cells

Comments

Supplementary Materials

Data Availability Statement

PMID: 36362214