Genetic defects of gamma‐secretase genes in a multiple myeloma patient with high and dysregulated BCMA surface density: A case report-Reference-Cited by-同舟云学术

Genetic defects of gamma‐secretase genes in a multiple myeloma patient with high and dysregulated BCMA surface density: A case report

Published:2023-11-13 Issue: Volume: Page:
ISSN:0007-1048
Container-title:British Journal of Haematology
language:en
Short-container-title:Br J Haematol

Author:

Cattaneo Irene¹^ORCID,Valgardsdottir Rut¹,Cavagna Roberta²,Spinelli Orietta²,Bartoletti‐Stella Anna³,Capellari Sabina⁴⁵,Galli Monica²,Golay Josée¹^ORCID

Affiliation:

1. Center of Cellular Therapy “G. Lanzani” ASST Papa Giovanni XXIII Bergamo Italy

2. Division of Hematology ASST Papa Giovanni XXIII Bergamo Italy

3. Department of Medical and Surgical Sciences (DIMEC) University of Bologna Bologna Italy

4. IRCCS Istituto delle Scienze Neurologiche di Bologna Bellaria Hospital Bologna Italy

5. Department of Biomedical and NeuroMotor Sciences (DIBINEM) University of Bologna Bologna Italy

Abstract

SummaryMultiple myeloma (MM) cells from 1 out of 20 patient expressed high basal levels of membrane B‐cell maturation antigen (BCMA, TNFRSF17, CD269), which was not upregulated by gamma‐secretase inhibitor, suggesting a defective BCMA shedding by gamma‐secretase. Genetic analyses of the patient's bone marrow DNA showed no mutations within the BCMA coding region, but rather partial deletion of PSEN1 and amplification of PSEN2, which encode alternative catalytic units of gamma‐secretase. Altogether the data suggest that pt#12 MM cells express high and dysregulated BCMA with no shedding, due to genetic alterations of one or more gamma‐secretase subunits.

Funder

Associazione Italiana per la Ricerca sul Cancro

Publisher

Wiley

Subject

Hematology

Link

https://onlinelibrary.wiley.com/doi/pdf/10.1111/bjh.19168

Reference16 articles.

1. γ‐Secretase directly sheds the survival receptor BCMA from plasma cells;Laurent SA;Nat Commun,2015

2. Quantification of B‐cell maturation antigen, a target for novel chimeric antigen receptor T‐cell therapy in myeloma;Salem DA;Leuk Res,2018

3. The substrate repertoire of γ‐secretase/presenilin;Güner G;Semin Cell Dev Biol,2020

4. Targeted sequencing panels in Italian ALS patients support different etiologies in the ALS/FTD continuum;Bartoletti‐Stella A;J Neurol,2021

5. Analysis of the 5′ sequence, genomic structure, and alternative splicing of the presenilin‐1 gene (PSEN1) associated with early onset Alzheimer disease;Rogaev EI;Genomics,1997

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1. Soluble B‐cell maturation antigen in multiple myeloma;American Journal of Hematology;2024-01-25

2. Unveiling the link between genetic alterations in gamma secretase and BCMA surface density in multiple myeloma;British Journal of Haematology;2023-11-28