{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T00:18:05Z","timestamp":1791850685497,"version":"4.3.4"},"reference-count":41,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2023,9,4]],"date-time":"2023-09-04T00:00:00Z","timestamp":1693785600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Chronic lymphocytic leukemia (CLL) co\u2010evolves with its own microenvironment where inflammatory stimuli including toll\u2010like receptors (TLR) signaling can protect CLL cells from spontaneous and drug\u2010induced apoptosis by upregulating I\u03baB\u03b6, an atypical co\u2010transcription factor. To dissect I\u03baB\u03b6\u2010centered signaling pathways, we performed a gene expression profile of primary leukemic cells expressing either high or low levels of I\u03baB\u03b6 after stimulation, highlighting that I\u03baB\u03b6 is not only an inflammatory gene but it may control metabolic rewiring of malignant cells thus pointing to a novel potential opportunity for therapy. We exploited the capacity of the dimethyl itaconate (DI), an anti\u2010inflammatory electrophilic synthetic derivative of the metabolite Itaconate, to target I\u03baB\u03b6. CLL cells, murine leukemic splenocytes, and leukocytes from healthy donors were treated\n                    <jats:italic>in vitro<\/jats:italic>\n                    with DI that abolished metabolic activation and reduced cell viability of leukemic cells only, even in the presence of robust TLR prestimulation. RNA sequencing highlighted that in addition to the expected electrophilic stress signature observed after DI treatment, novel pathways emerged including the downregulation of distinct MHC class II complex genes. In conclusion, DI not only abrogated the proinflammatory effects of TLR stimulation but also targeted a specific metabolic vulnerability in CLL cells.\n                  <\/jats:p>","DOI":"10.1002\/eji.202350418","type":"journal-article","created":{"date-parts":[[2023,8,10]],"date-time":"2023-08-10T16:09:10Z","timestamp":1691683750000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Dimethyl itaconate selectively targets inflammatory and metabolic pathways in chronic lymphocytic leukemia"],"prefix":"10.1002","volume":"53","author":[{"given":"Ilenia","family":"Sana","sequence":"first","affiliation":[{"name":"Cell signaling Unit, Division of Experimental Oncology IRCCS San Raffaele Scientific Institute  Milano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Elena","family":"Mantione","sequence":"additional","affiliation":[{"name":"Cell signaling Unit, Division of Experimental Oncology IRCCS San Raffaele Scientific Institute  Milano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Meloni","sequence":"additional","affiliation":[{"name":"Cell signaling Unit, Division of Experimental Oncology IRCCS San Raffaele Scientific Institute  Milano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michela","family":"Riba","sequence":"additional","affiliation":[{"name":"Center for Omics Sciences IRCCS San Raffaele Scientific Institute  Milano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela","family":"Ranghetti","sequence":"additional","affiliation":[{"name":"B\u2010cell neoplasia Unit Division of Experimental Oncology IRCCS San Raffaele Scientific Institute  Milano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lydia","family":"Scarf\u00f2","sequence":"additional","affiliation":[{"name":"B\u2010cell neoplasia Unit Division of Experimental Oncology IRCCS San Raffaele Scientific Institute  Milano Italy"},{"name":"Vita\u2010Salute San Raffaele University  Milano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Ghia","sequence":"additional","affiliation":[{"name":"B\u2010cell neoplasia Unit Division of Experimental Oncology IRCCS San Raffaele Scientific Institute  Milano Italy"},{"name":"Vita\u2010Salute San Raffaele University  Milano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Muzio","sequence":"additional","affiliation":[{"name":"Cell signaling Unit, Division of Experimental Oncology IRCCS San Raffaele Scientific Institute  Milano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,9,4]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-019-0239-8"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-18-0781"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.15252\/msb.202110855"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2404417"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020005964"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.leukres.2009.12.020"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0228674"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.2741\/4108"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2012.44"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-12-1922"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2017.165878"},{"key":"e_1_2_9_13_1","first-page":"66310","article-title":"I\u03baB\u03b6: an emerging player in cancer","volume":"4","author":"Willems M.","year":"2016","journal-title":"Onco. 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