{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T22:25:02Z","timestamp":1790115902807,"version":"4.0.1"},"reference-count":37,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,6,11]],"date-time":"2025-06-11T00:00:00Z","timestamp":1749600000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["R21-AG070502"],"award-info":[{"award-number":["R21-AG070502"]}]},{"name":"NIH","award":["R01-CA279808"],"award-info":[{"award-number":["R01-CA279808"]}]},{"name":"Janssen QuickFire Challenge Idea Grant","award":["R21-AG070502"],"award-info":[{"award-number":["R21-AG070502"]}]},{"name":"Janssen QuickFire Challenge Idea Grant","award":["R01-CA279808"],"award-info":[{"award-number":["R01-CA279808"]}]},{"name":"Tufts Medicine Myeloma and Amyloid Research Fund","award":["R21-AG070502"],"award-info":[{"award-number":["R21-AG070502"]}]},{"name":"Tufts Medicine Myeloma and Amyloid Research Fund","award":["R01-CA279808"],"award-info":[{"award-number":["R01-CA279808"]}]},{"name":"Sidewater Family Fund","award":["R21-AG070502"],"award-info":[{"award-number":["R21-AG070502"]}]},{"name":"Sidewater Family Fund","award":["R01-CA279808"],"award-info":[{"award-number":["R01-CA279808"]}]},{"name":"Amyloidosis Foundation","award":["R21-AG070502"],"award-info":[{"award-number":["R21-AG070502"]}]},{"name":"Amyloidosis Foundation","award":["R01-CA279808"],"award-info":[{"award-number":["R01-CA279808"]}]},{"name":"David and Barbara Levine","award":["R21-AG070502"],"award-info":[{"award-number":["R21-AG070502"]}]},{"name":"David and Barbara Levine","award":["R01-CA279808"],"award-info":[{"award-number":["R01-CA279808"]}]},{"name":"Mackenzie\u2019s Mission","award":["R21-AG070502"],"award-info":[{"award-number":["R21-AG070502"]}]},{"name":"Mackenzie\u2019s Mission","award":["R01-CA279808"],"award-info":[{"award-number":["R01-CA279808"]}]},{"name":"Demarest Lloyd Jr. Foundation","award":["R21-AG070502"],"award-info":[{"award-number":["R21-AG070502"]}]},{"name":"Demarest Lloyd Jr. Foundation","award":["R01-CA279808"],"award-info":[{"award-number":["R01-CA279808"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background\/Objectives: To reduce the early mortality of light-chain amyloidosis (AL), earlier diagnosis is needed. To pursue this goal, we conducted a multicenter study screening for AL \u03bb-type (NCT04615572) in subjects &gt; 60 years of age with \u03bb smoldering myeloma (SMM) or monoclonal gammopathy of undetermined significance (MGUS), a light-chain differential (dFLC, \u03bb minus \u03ba) &gt; 23 mg\/L, and no prior amyloid diagnosis. Methods: Variables included AL-related IGVL gene usage and clonal plasma cell cytogenetic abnormalities, such as t(11;14) or gain 1q, which are present in 75% of AL cases. Here, 9 out of 33 \u03bb IGVL genes, accounting for 90% of AL \u03bb cases, were considered to be AL-related. Bone marrow was obtained, plasma cell cytogenetics and next generation sequencing for IGVL genes were performed, and subjects with AL-related IGVL genes were screened for AL using tissue studies. Results: From 2021 to 2023, we enrolled 30 subjects (19 M\/11 F) with a median age of 68.5 years old (IQR 64.3\u201373), 17 SMM and 13 MGUS, with a median of 6% marrow plasma cells (range, 3.5\u201340). Here, 11 SMM and 4 MGUS cases had t(11;14) or gain 1q; 10\/17 SMM and 12\/13 MGUS had AL-related genes, and AL was ultimately confirmed by tissue biopsy in 3 with SMM. SMM, AL-related IGVL genes, and t(11;14) or gain 1q were found in 6 SMM subjects, including the 3 with AL (3\/6 vs. 0\/16; p &lt; 0.05, Fisher\u2019s exact, two-tailed). Conclusions: These results justify a larger study screening for AL in SMM to develop a likelihood algorithm for AL using dFLC, IGVL gene usage, and the presence of t(11;14) or gain 1q.<\/jats:p>","DOI":"10.3390\/jcm14124146","type":"journal-article","created":{"date-parts":[[2025,6,11]],"date-time":"2025-06-11T11:18:40Z","timestamp":1749640720000},"page":"4146","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Screening for Systemic Light-Chain Amyloidosis in Patients Over 60 with \u03bb Monoclonal Gammopathies"],"prefix":"10.3390","volume":"14","author":[{"given":"Ping","family":"Zhou","sequence":"first","affiliation":[{"name":"The Tufts Medicine Myeloma and Amyloid Program, Tufts Medical Center, 800 Washington Street, P.O. Box 826, Boston, MA 02111, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2044-0751","authenticated-orcid":false,"given":"Mahesh M.","family":"Mansukhani","sequence":"additional","affiliation":[{"name":"Columbia University Laboratory of Personalized Genomic Medicine, Department of Pathology & Cell Biology, Columbia University Irving Medical Center (CUIMC), New York, NY 10032, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond","family":"Yeh","sequence":"additional","affiliation":[{"name":"Columbia University Laboratory of Personalized Genomic Medicine, Department of Pathology & Cell Biology, Columbia University Irving Medical Center (CUIMC), New York, NY 10032, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiesheng","family":"Lu","sequence":"additional","affiliation":[{"name":"Columbia University Laboratory of Personalized Genomic Medicine, Department of Pathology & Cell Biology, Columbia University Irving Medical Center (CUIMC), New York, NY 10032, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongai","family":"Xia","sequence":"additional","affiliation":[{"name":"Columbia University Laboratory of Personalized Genomic Medicine, Department of Pathology & Cell Biology, Columbia University Irving Medical Center (CUIMC), New York, NY 10032, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lahari","family":"Koganti","sequence":"additional","affiliation":[{"name":"Columbia University Laboratory of Personalized Genomic Medicine, Department of Pathology & Cell Biology, Columbia University Irving Medical Center (CUIMC), New York, NY 10032, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiuhong","family":"Pang","sequence":"additional","affiliation":[{"name":"Columbia University Laboratory of Personalized Genomic Medicine, Department of Pathology & Cell Biology, Columbia University Irving Medical Center (CUIMC), New York, NY 10032, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denis","family":"Toskic","sequence":"additional","affiliation":[{"name":"The Tufts Medicine Myeloma and Amyloid Program, Tufts Medical Center, 800 Washington Street, P.O. Box 826, Boston, MA 02111, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Scalia","sequence":"additional","affiliation":[{"name":"The Tufts Medicine Myeloma and Amyloid Program, Tufts Medical Center, 800 Washington Street, P.O. Box 826, Boston, MA 02111, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xun","family":"Ma","sequence":"additional","affiliation":[{"name":"The Tufts Medicine Myeloma and Amyloid Program, Tufts Medical Center, 800 Washington Street, P.O. Box 826, Boston, MA 02111, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa X.","family":"Lee","sequence":"additional","affiliation":[{"name":"Chao Family Comprehensive Cancer Center, University of California, Orange, Irvine, CA 92617, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandy W.","family":"Wong","sequence":"additional","affiliation":[{"name":"Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 94143, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfred","family":"Chung","sequence":"additional","affiliation":[{"name":"Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 94143, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2109-1573","authenticated-orcid":false,"given":"Sascha A.","family":"Tuchman","sequence":"additional","affiliation":[{"name":"Multiple Myeloma and Amyloidosis Program, Division of Hematology, Department of Medicine, University of North Carolina, Chapel Hill, NC 27599, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terry","family":"Fogaren","sequence":"additional","affiliation":[{"name":"The Tufts Medicine Myeloma and Amyloid Program, Tufts Medical Center, 800 Washington Street, P.O. Box 826, Boston, MA 02111, USA"},{"name":"Division of Hematology-Oncology, Department of Medicine, Tufts Medical Center, Boston, MA 02111, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy","family":"Coady Lyons","sequence":"additional","affiliation":[{"name":"The Tufts Medicine Myeloma and Amyloid Program, Tufts Medical Center, 800 Washington Street, P.O. Box 826, Boston, MA 02111, USA"},{"name":"Division of Hematology-Oncology, Department of Medicine, Tufts Medical Center, Boston, MA 02111, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cindy","family":"Varga","sequence":"additional","affiliation":[{"name":"The Tufts Medicine Myeloma and Amyloid Program, Tufts Medical Center, 800 Washington Street, P.O. Box 826, Boston, MA 02111, USA"},{"name":"Division of Hematology-Oncology, Department of Medicine, Tufts Medical Center, Boston, MA 02111, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne","family":"Lentzsch","sequence":"additional","affiliation":[{"name":"Multiple Myeloma and Amyloidosis Service, CUIMC, New York, NY 10032, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6255-5824","authenticated-orcid":false,"given":"Raymond L.","family":"Comenzo","sequence":"additional","affiliation":[{"name":"The Tufts Medicine Myeloma and Amyloid Program, Tufts Medical Center, 800 Washington Street, P.O. Box 826, Boston, MA 02111, USA"},{"name":"Division of Hematology-Oncology, Department of Medicine, Tufts Medical Center, Boston, MA 02111, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1056\/NEJMoa2028631","article-title":"Daratumumab-Based Treatment for Immunoglobulin Light-Chain Amyloidosis","volume":"385","author":"Kastritis","year":"2021","journal-title":"N. Engl. J. 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