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Characterization of BCMA Expression in Circulating Rare Single Cells of Patients with Plasma Cell Neoplasms
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....
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9658574/ https://www.ncbi.nlm.nih.gov/pubmed/36362214 http://dx.doi.org/10.3390/ijms232113427 |
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author | Ndacayisaba, Libere J. Rappard, Kate E. Shishido, Stephanie N. Setayesh, Sonia M. Tang, Guilin Lin, Pei Matsumoto, Nicholas Hsu, Ching-Ju Nevarez, Rafael Velasco, Carmen Ruiz Naghdloo, Amin Yang, Eric Kelly, Kevin Hicks, James Mason, Jeremy Orlowski, Robert Z. Manasanch, Elisabet E. Kuhn, Peter |
author_facet | Ndacayisaba, Libere J. Rappard, Kate E. Shishido, Stephanie N. Setayesh, Sonia M. Tang, Guilin Lin, Pei Matsumoto, Nicholas Hsu, Ching-Ju Nevarez, Rafael Velasco, Carmen Ruiz Naghdloo, Amin Yang, Eric Kelly, Kevin Hicks, James Mason, Jeremy Orlowski, Robert Z. Manasanch, Elisabet E. Kuhn, Peter |
author_sort | Ndacayisaba, Libere J. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9658574 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-96585742022-11-15 Characterization of BCMA Expression in Circulating Rare Single Cells of Patients with Plasma Cell Neoplasms Ndacayisaba, Libere J. Rappard, Kate E. Shishido, Stephanie N. Setayesh, Sonia M. Tang, Guilin Lin, Pei Matsumoto, Nicholas Hsu, Ching-Ju Nevarez, Rafael Velasco, Carmen Ruiz Naghdloo, Amin Yang, Eric Kelly, Kevin Hicks, James Mason, Jeremy Orlowski, Robert Z. Manasanch, Elisabet E. Kuhn, Peter Int J Mol Sci Article 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. MDPI 2022-11-03 /pmc/articles/PMC9658574/ /pubmed/36362214 http://dx.doi.org/10.3390/ijms232113427 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Ndacayisaba, Libere J. Rappard, Kate E. Shishido, Stephanie N. Setayesh, Sonia M. Tang, Guilin Lin, Pei Matsumoto, Nicholas Hsu, Ching-Ju Nevarez, Rafael Velasco, Carmen Ruiz Naghdloo, Amin Yang, Eric Kelly, Kevin Hicks, James Mason, Jeremy Orlowski, Robert Z. Manasanch, Elisabet E. Kuhn, Peter Characterization of BCMA Expression in Circulating Rare Single Cells of Patients with Plasma Cell Neoplasms |
title | Characterization of BCMA Expression in Circulating Rare Single Cells of Patients with Plasma Cell Neoplasms |
title_full | Characterization of BCMA Expression in Circulating Rare Single Cells of Patients with Plasma Cell Neoplasms |
title_fullStr | Characterization of BCMA Expression in Circulating Rare Single Cells of Patients with Plasma Cell Neoplasms |
title_full_unstemmed | Characterization of BCMA Expression in Circulating Rare Single Cells of Patients with Plasma Cell Neoplasms |
title_short | Characterization of BCMA Expression in Circulating Rare Single Cells of Patients with Plasma Cell Neoplasms |
title_sort | characterization of bcma expression in circulating rare single cells of patients with plasma cell neoplasms |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9658574/ https://www.ncbi.nlm.nih.gov/pubmed/36362214 http://dx.doi.org/10.3390/ijms232113427 |
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