Cargando…

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....

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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
_version_ 1784829984966180864
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
work_keys_str_mv AT ndacayisabaliberej characterizationofbcmaexpressionincirculatingraresinglecellsofpatientswithplasmacellneoplasms
AT rappardkatee characterizationofbcmaexpressionincirculatingraresinglecellsofpatientswithplasmacellneoplasms
AT shishidostephanien characterizationofbcmaexpressionincirculatingraresinglecellsofpatientswithplasmacellneoplasms
AT setayeshsoniam characterizationofbcmaexpressionincirculatingraresinglecellsofpatientswithplasmacellneoplasms
AT tangguilin characterizationofbcmaexpressionincirculatingraresinglecellsofpatientswithplasmacellneoplasms
AT linpei characterizationofbcmaexpressionincirculatingraresinglecellsofpatientswithplasmacellneoplasms
AT matsumotonicholas characterizationofbcmaexpressionincirculatingraresinglecellsofpatientswithplasmacellneoplasms
AT hsuchingju characterizationofbcmaexpressionincirculatingraresinglecellsofpatientswithplasmacellneoplasms
AT nevarezrafael characterizationofbcmaexpressionincirculatingraresinglecellsofpatientswithplasmacellneoplasms
AT velascocarmenruiz characterizationofbcmaexpressionincirculatingraresinglecellsofpatientswithplasmacellneoplasms
AT naghdlooamin characterizationofbcmaexpressionincirculatingraresinglecellsofpatientswithplasmacellneoplasms
AT yangeric characterizationofbcmaexpressionincirculatingraresinglecellsofpatientswithplasmacellneoplasms
AT kellykevin characterizationofbcmaexpressionincirculatingraresinglecellsofpatientswithplasmacellneoplasms
AT hicksjames characterizationofbcmaexpressionincirculatingraresinglecellsofpatientswithplasmacellneoplasms
AT masonjeremy characterizationofbcmaexpressionincirculatingraresinglecellsofpatientswithplasmacellneoplasms
AT orlowskirobertz characterizationofbcmaexpressionincirculatingraresinglecellsofpatientswithplasmacellneoplasms
AT manasanchelisabete characterizationofbcmaexpressionincirculatingraresinglecellsofpatientswithplasmacellneoplasms
AT kuhnpeter characterizationofbcmaexpressionincirculatingraresinglecellsofpatientswithplasmacellneoplasms