{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T18:29:39Z","timestamp":1780511379681,"version":"3.54.1"},"reference-count":46,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"758","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2024,7,31]]},"abstract":"<jats:p>\n            Richter\u2019s transformation (RT) is a progression of chronic lymphocytic leukemia (CLL) to aggressive lymphoma.\n            <jats:italic>MGA<\/jats:italic>\n            (\n            <jats:italic>Max gene associated<\/jats:italic>\n            ), a functional MYC suppressor, is mutated at 3% in CLL and 36% in RT. However, genetic models and molecular mechanisms of\n            <jats:italic>MGA<\/jats:italic>\n            deletion that drive CLL to RT remain elusive. We established an RT mouse model by knockout of\n            <jats:italic>Mga<\/jats:italic>\n            in the\n            <jats:italic>Sf3b1<\/jats:italic>\n            \/\n            <jats:italic>Mdr<\/jats:italic>\n            CLL model using CRISPR-Cas9 to determine the role of\n            <jats:italic>Mga<\/jats:italic>\n            in RT. Murine RT cells exhibited mitochondrial aberrations with elevated oxidative phosphorylation (OXPHOS). Through RNA sequencing and functional characterization, we identified\n            <jats:italic>Nme1<\/jats:italic>\n            (nucleoside diphosphate kinase) as an\n            <jats:italic>Mga<\/jats:italic>\n            target, which drives RT by modulating OXPHOS. Given that\n            <jats:italic>NME1<\/jats:italic>\n            is also a known MYC target without targetable compounds, we found that concurrent inhibition of MYC and electron transport chain complex II substantially prolongs the survival of RT mice in vivo. Our results suggest that the\n            <jats:italic>Mga-Nme1<\/jats:italic>\n            axis drives murine CLL-to-RT transition via modulating OXPHOS, highlighting a potential therapeutic avenue for RT.\n          <\/jats:p>","DOI":"10.1126\/scitranslmed.adg7915","type":"journal-article","created":{"date-parts":[[2024,7,31]],"date-time":"2024-07-31T18:05:15Z","timestamp":1722449115000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":14,"title":["<i>MGA<\/i>\n            deletion leads to Richter\u2019s transformation by modulating mitochondrial OXPHOS"],"prefix":"10.1126","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6982-6343","authenticated-orcid":true,"given":"Prajish","family":"Iyer","sequence":"first","affiliation":[{"name":"Department of Systems Biology, Beckman Research Institute, City of Hope National Comprehensive Cancer Center, Monrovia, CA 91016, 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USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7567-1744","authenticated-orcid":true,"given":"Kevyn","family":"Hart","sequence":"additional","affiliation":[{"name":"Department of Systems Biology, Beckman Research Institute, City of Hope National Comprehensive Cancer Center, Monrovia, CA 91016, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3099-6665","authenticated-orcid":true,"given":"Jibin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Hematology &amp; Hematopoietic Cell Transplantation, City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA."},{"name":"Toni Stephenson Lymphoma Center, Beckman Research Institute, City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viola","family":"Siegert","sequence":"additional","affiliation":[{"name":"Institute of Clinical Chemistry and Pathobiochemistry, TUM School of Medicine and Health, Technical University of Munich, Munich 81675, Germany."},{"name":"Central Institute for Translational Cancer Research, Technische Universit\u00e4t M\u00fcnchen, Munich 81675, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1363-4737","authenticated-orcid":true,"given":"Marianne","family":"Remke","sequence":"additional","affiliation":[{"name":"Institute of Pathology, TUM School of Medicine and Health, Technical University of Munich, Munich 81675, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuesong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Botany and Plant Sciences, University of California, Riverside, CA 92507, USA."},{"name":"Graduate Program in Genetics, Genomics, and Bioinformatics, University of California, Riverside, CA 92507, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7817-5319","authenticated-orcid":true,"given":"Lei","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Botany and Plant Sciences, University of California, Riverside, CA 92507, USA."},{"name":"Graduate Program in Genetics, Genomics, and Bioinformatics, University of California, Riverside, CA 92507, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3497-2513","authenticated-orcid":true,"given":"Joo","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Hematology &amp; Hematopoietic Cell Transplantation, City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA."},{"name":"Toni Stephenson Lymphoma Center, Beckman Research Institute, City of Hope Comprehensive Cancer Center, Duarte, CA 91010, 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