{"doi":"10.1111/bjh.19168","title":"Genetic defects of gamma‐secretase genes in a multiple myeloma patient with high and dysregulated BCMA surface density: A case report","abstract":"<jats:title>Summary</jats:title><jats:p>Multiple 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 <jats:italic>PSEN1</jats:italic> and amplification of <jats:italic>PSEN2</jats:italic>, 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.</jats:p>","journal":"British Journal of Haematology","year":2024,"id":620592,"datarank":0.26876392038420827,"base_score":1.791759469228055,"endowment":1.791759469228055,"self_citation_contribution":0.26876392038420827,"citation_network_contribution":0.0,"self_endowment_contribution":0.26876392038420827,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1602091,"name":"Rut Valgardsdottir","orcid":null,"position":1,"is_corresponding":false},{"id":1602092,"name":"Roberta Cavagna","orcid":null,"position":2,"is_corresponding":false},{"id":318313,"name":"Orietta Spinelli","orcid":"0000-0003-0374-1536","position":3,"is_corresponding":false},{"id":300794,"name":"Anna Bartoletti‐Stella","orcid":"0000-0001-6442-162X","position":4,"is_corresponding":false},{"id":227551,"name":"Sabina Capellari","orcid":"0000-0003-1631-1439","position":5,"is_corresponding":false},{"id":1587096,"name":"Monica Galli","orcid":null,"position":6,"is_corresponding":false},{"id":1602093,"name":"Josée Golay","orcid":"0000-0002-7932-909X","position":7,"is_corresponding":false},{"id":1602090,"name":"Irene Cattaneo","orcid":"0000-0002-5094-7150","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Genetic defects of gamma‐secretase genes in a multiple myeloma patient with high and dysregulated BCMA surface density: A case report","abstract":"<jats:title>Summary</jats:title><jats:p>Multiple 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 <jats:italic>PSEN1</jats:italic> and amplification of <jats:italic>PSEN2</jats:italic>, 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.</jats:p>","is_dataset_classified":null,"base_score":1.791759469228055,"endowment":1.791759469228055,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"37957838","pmcid":null,"openalex_id":"https://openalex.org/W4388671199","authors":[],"funders":[{"funder_name":"Associazione Italiana per la Ricerca sul Cancro","grant_id":"21147","title":null},{"funder_name":"Associazione Italiana contro le Leucemie, linfoma e mieloma (AIL-sezione Paolo Belli, Bergamo)","grant_id":"","title":null}],"total_grants":2,"fwci":0.9185,"citation_percentile":0.75847937,"influential_citations":0,"citation_trend":[{"year":2023,"count":1},{"year":2024,"count":1},{"year":2025,"count":3}],"oa_status":"bronze","license":"http://onlinelibrary.wiley.com/termsAndConditions#vor","oa_locations":[{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/bjh.19168","host_type":"journal"},{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/bjh.19168","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/pdf/10.1111/bjh.19168","host_type":"publisher"},{"url":"https://doi.org/10.1111/bjh.19168","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/37957838","host_type":"repository"},{"url":"https://hdl.handle.net/11585/1000992","host_type":"repository"}],"fields_of_study":["Multiple Myeloma Research and Treatments","Monoclonal and Polyclonal Antibodies Research","Chronic Myeloid Leukemia Treatments"],"mesh_terms":["Bone Marrow","Humans","Multiple Myeloma","B-Cell Maturation Antigen","Amyloid Precursor Protein Secretases"],"keywords":["PSEN1","Cancer research","Multiple myeloma","Gamma secretase","Bone marrow","Gene","Biology","Neprilysin","Molecular biology","Cell biology","Medicine","Genetics","Immunology","Pathology","Amyloid precursor protein","Biochemistry","Enzyme","Alzheimer's disease","BCMA","Genetic Alterations","Presenilins"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-03T11:31:48.011853Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}