{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T01:38:38Z","timestamp":1789609118982,"version":"build-2803163510"},"reference-count":40,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,6,10]],"date-time":"2022-06-10T00:00:00Z","timestamp":1654819200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Carfilzomib, an irreversible proteasome inhibitor approved for the treatment of relapsed\/refractory Multiple Myeloma (MM) has been associated with Thrombotic Microangiopathy (TMA). Several pathogenetic mechanisms of carfilzomib-induced TMA have been proposed; however, recently, there has been a shift of focus on the potential contribution of complement dysregulation. Our aim was to explore whether patients with carfilzomib-induced TMA harbor germline variants of complement-related genes, which have been characterized as risk factors for TMA. Methods: We retrospectively recruited consecutive MM patients with carfilzomib-induced TMA and compared them to MM patients who received \u22654 cycles of carfilzomib and did not develop signs\/symptoms of TMA, in a 1:2 ratio. Genomic DNA from peripheral blood was analyzed using next generation sequencing (NGS) with a complement-related gene panel; ADAMTS13 activity and soluble C5b-9 were measured using ELISA. Results: Complement-related variants were more common in patients with carfilzomib-induced TMA compared to non-TMA controls, regardless of patient and treatment characteristics; ADAMTS13 activity and C5b-9 were compatible with the phenotype of complement-related TMA. Conclusions: We confirmed the previous findings that implicated complement-related genes in the pathogenesis of carfilzomib-induced TMA. Most importantly, by incorporating a control group of non-TMA MM patients treated with carfilzomib-based regimens and functional complement assays, we enhanced the credibility of our findings.<\/jats:p>","DOI":"10.3390\/jcm11123355","type":"journal-article","created":{"date-parts":[[2022,6,10]],"date-time":"2022-06-10T10:25:12Z","timestamp":1654856712000},"page":"3355","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Genetic and Functional Evidence of Complement Dysregulation in Multiple Myeloma Patients with Carfilzomib-Induced Thrombotic Microangiopathy Compared to Controls"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8883-8208","authenticated-orcid":false,"given":"Eleni","family":"Gavriilaki","sequence":"first","affiliation":[{"name":"Hematology Department\u2014BMT Unit, G. Papanicolaou Hospital, 570 10 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitra","family":"Dalampira","sequence":"additional","affiliation":[{"name":"Hematology Department, Theagenio Cancer Hospital, 546 39 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6926-0351","authenticated-orcid":false,"given":"Foteini","family":"Theodorakakou","sequence":"additional","affiliation":[{"name":"Department of Clinical Therapeutics, National and Kapodistrian University of Athens, 115 28 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine-Ivy","family":"Liacos","sequence":"additional","affiliation":[{"name":"Department of Clinical Therapeutics, National and Kapodistrian University of Athens, 115 28 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolaos","family":"Kanellias","sequence":"additional","affiliation":[{"name":"Department of Clinical Therapeutics, National and Kapodistrian University of Athens, 115 28 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3407-5994","authenticated-orcid":false,"given":"Evangelos","family":"Eleutherakis-Papaiakovou","sequence":"additional","affiliation":[{"name":"Department of Clinical Therapeutics, National and Kapodistrian University of Athens, 115 28 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5133-1422","authenticated-orcid":false,"given":"Evangelos","family":"Terpos","sequence":"additional","affiliation":[{"name":"Department of Clinical Therapeutics, National and Kapodistrian University of Athens, 115 28 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Gavriatopoulou","sequence":"additional","affiliation":[{"name":"Department of Clinical Therapeutics, National and Kapodistrian University of Athens, 115 28 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evgenia","family":"Verrou","sequence":"additional","affiliation":[{"name":"Hematology Department, Theagenio Cancer Hospital, 546 39 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theodora","family":"Triantafyllou","sequence":"additional","affiliation":[{"name":"Hematology Department, Theagenio Cancer Hospital, 546 39 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aggeliki","family":"Sevastoudi","sequence":"additional","affiliation":[{"name":"Hematology Department, Theagenio Cancer Hospital, 546 39 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evaggelia-Evdoxia","family":"Koravou","sequence":"additional","affiliation":[{"name":"Hematology Department\u2014BMT Unit, G. Papanicolaou Hospital, 570 10 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tasoula","family":"Touloumenidou","sequence":"additional","affiliation":[{"name":"Hematology Department\u2014BMT Unit, G. Papanicolaou Hospital, 570 10 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3809-0761","authenticated-orcid":false,"given":"Christos","family":"Varelas","sequence":"additional","affiliation":[{"name":"Hematology Department\u2014BMT Unit, G. Papanicolaou Hospital, 570 10 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Apostolia","family":"Papalexandri","sequence":"additional","affiliation":[{"name":"Hematology Department\u2014BMT Unit, G. Papanicolaou Hospital, 570 10 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioanna","family":"Sakellari","sequence":"additional","affiliation":[{"name":"Hematology Department\u2014BMT Unit, G. Papanicolaou Hospital, 570 10 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8990-3254","authenticated-orcid":false,"given":"Meletios A.","family":"Dimopoulos","sequence":"additional","affiliation":[{"name":"Department of Clinical Therapeutics, National and Kapodistrian University of Athens, 115 28 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8191-5832","authenticated-orcid":false,"given":"Efstathios","family":"Kastritis","sequence":"additional","affiliation":[{"name":"Department of Clinical Therapeutics, National and Kapodistrian University of Athens, 115 28 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9404-807X","authenticated-orcid":false,"given":"Eirini","family":"Katodritou","sequence":"additional","affiliation":[{"name":"Hematology Department, Theagenio Cancer Hospital, 546 39 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1002\/ajh.25791","article-title":"Multiple myeloma: 2020 update on diagnosis, risk-stratification and management","volume":"95","author":"Rajkumar","year":"2020","journal-title":"Am. 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