{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T09:18:53Z","timestamp":1780046333298,"version":"3.53.1"},"reference-count":29,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,12,21]],"date-time":"2025-12-21T00:00:00Z","timestamp":1766275200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,12,21]],"date-time":"2025-12-21T00:00:00Z","timestamp":1766275200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100018866","name":"Paula and Rodger Riney Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100018866","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["European J of Haematology"],"published-print":{"date-parts":[[2026,4]]},"abstract":"ABSTRACT<\/jats:title>\n \n Background<\/jats:title>\n \n Immunomodulatory agents (IMiDs) are a cornerstone in the successful management of multiple myeloma (MM). However, acquired IMiD resistance leading to disease relapses remains a major barrier. Hydrogen peroxide generation and oxidative stress are key mediators that determine IMiD's effectiveness in MM. Iron plays a key role in the generation of oxidative stress; therefore, cellular iron levels are tightly governed.\n FTH1<\/jats:italic>\n is the major iron storage protein that tightly regulates cellular iron availability. Hence, the present study is targeted to investigate the role of\n FTH1<\/jats:italic>\n in MM and IMiD resistance.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n IMiD\u2010sensitive and IMiD\u2010resistant MM cells were analyzed for expression of iron\u2010metabolism genes. CRISPR\u2010cas9\u2010mediated knockout of\n FTH1<\/jats:italic>\n was performed and the after\u2010effects were assessed through multiple experiments.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Initial analysis showed a positive correlation between\n FTH1<\/jats:italic>\n expression and IMiD resistance in MM cells.\n FTH1<\/jats:italic>\n \u2010KO reduced IMiD sensitivity in the KMS11 cell line but had no effect on the RPMI8226 cell line. RNA\u2010seq data showed downregulation of ER\u2010stress and calcium signaling genes after\n FTH1<\/jats:italic>\n \u2010KO. Further, KMS11\u2010\n FTH1<\/jats:italic>\n KO cells exhibited lower intracellular ROS, labile\u2010iron, and mitochondrial superoxide levels along with increased CD63, suggesting activation of L\u2010ferritin secretory pathways.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n Data reveals a link between\n FTH1<\/jats:italic>\n , labile iron, ROS, and IMiD resistance in MM cells.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/ejh.70084","type":"journal-article","created":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T01:16:02Z","timestamp":1766366162000},"page":"391-401","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ferritin H<\/i>\n Knockout Induces Differential Immunomodulatory Drug Responses in Multiple Myeloma Cell Lines"],"prefix":"10.1111","volume":"116","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8744-1268","authenticated-orcid":false,"given":"Aarti","family":"Sharma","sequence":"first","affiliation":[{"name":"Mayo Clinic in Arizona Phoenix Arizona USA"},{"name":"Department of Nephrology Indian Institute of Science Bengaluru Karnataka India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Latha","family":"Pathangey","sequence":"additional","affiliation":[{"name":"Mayo Clinic in Arizona Phoenix Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sinto Sebastian","family":"Chirackal","sequence":"additional","affiliation":[{"name":"Division of Hematology and Medical Oncology Mayo Clinic Phoenix Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3448-9452","authenticated-orcid":false,"given":"Kevin G.","family":"Shim","sequence":"additional","affiliation":[{"name":"Division of Hematology and Medical Oncology Mayo Clinic Phoenix Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael","family":"Fonseca","sequence":"additional","affiliation":[{"name":"Division of Hematology and Medical Oncology Mayo Clinic Phoenix Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4773-141X","authenticated-orcid":false,"given":"Sundararaman","family":"Swaminathan","sequence":"additional","affiliation":[{"name":"Mayo Clinic in Arizona Phoenix Arizona USA"},{"name":"Department of Nephrology Indian Institute of Science Bengaluru Karnataka India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,21]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/medsci9010003"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-017-0689-1"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.1497"},{"issue":"2","key":"e_1_2_11_5_1","first-page":"131","article-title":"IMiD Resistance in Multiple Myeloma: Current Understanding of the Underpinning Biology and Clinical Impact","volume":"142","author":"Bird S.","year":"2023","journal-title":"Blood"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14164055"},{"issue":"1","key":"e_1_2_11_7_1","article-title":"CDK6 Protein Expression Is Associated With Disease Progression and Treatment Resistance in Multiple Myeloma","volume":"8","author":"Steinhart J.","year":"2024","journal-title":"Hema"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15041219"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41418-022-00943-y"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms222212234"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2023010335"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-09-738872"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V128.22.4482.4482"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-024-01969-z"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.3904\/kjim.2009.24.4.368"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2021010995"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbic.202100641"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2010.09.006"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.2174\/1381612825666190215121712"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/2211-5463.13303"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbcan.2023.188917"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24108852"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells10092431"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2017.10.005"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-021-03756-3"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/415092a"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2008.308"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceca.2017.08.004"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-019-1854-0"},{"issue":"3","key":"e_1_2_11_30_1","first-page":"306","article-title":"Prognostic Significance of Baseline Serum Ferritin in Newly Diagnosed Multiple Myeloma Cases: A Retrospective Study From Southern India","volume":"161","author":"Reshmy G. S.","year":"2025","journal-title":"Indian Journal of Medical Research"}],"container-title":["European Journal of Haematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ejh.70084","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/ejh.70084","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ejh.70084","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T08:47:58Z","timestamp":1780044478000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/ejh.70084"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,21]]},"references-count":29,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["10.1111\/ejh.70084"],"URL":"https:\/\/doi.org\/10.1111\/ejh.70084","archive":["Portico"],"relation":{},"ISSN":["0902-4441","1600-0609"],"issn-type":[{"value":"0902-4441","type":"print"},{"value":"1600-0609","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,21]]},"assertion":[{"value":"2025-08-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-02","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}