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Nevertheless, a subset of patients experiences refractory or relapsed disease, highlighting the need for new therapeutic strategies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Depmap database based on CRISPR\/Cas9 knock out analysis was employed to identify the essential gene SH3GL1, which encodes endophilin A2, as crucial for the proliferation and survival of DLBCL cells. Immunohistochemistry (IHC) staining was performed on the 126 paraffin\u2010embedded clinical DLBCL samples to investigate the association between SH3GL1 expression levels and the prognosis. To investigate the specific mechanism modulated by SH3GL1 in the progression of DLBCL, an integrative approach was employed. This approach combined high\u2010throughput sequencing technologies, such as Deep\u2010DIA and LC\u2010MS, with functional validation techniques, including CRISPR\/Cas9 gene editing, xenograft models, and molecular pathway analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Our study found that high expression levels of SH3GL1 correlate with poor prognosis in a cohort of 126 newly diagnosed DLBCL patients, underscoring its significance in disease progression. Mechanistically, we found that SH3GL1 deficiency triggers ferritin heavy chain 1 (FTH1)\u2010mediated ferroptosis, specifically ferritinophagy\u2010induced ferroptosis, in DLBCL cells. Additionally, high expression of SH3GL1 suppresses doxorubicin\u2010induced ferroptosis. Cancer cells' resistance to conventional therapies is associated with increased sensitivity to ferroptosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings emphasise SH3GL1 as a promising prognostic biomarker and a potential therapeutic target in DLBCL, offering new avenues for treatment strategies aimed at overcoming drug resistance and improving patients' outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Elevated SH3GL1 expression in DLBCL patients was associated with a negative prognosis.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>SH3GL1 plays a crucial role in promoting DLBCL cell survival through the regulation of FTH1\u2010mediated ferroptosis and doxorubicin resistance.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ctm2.70246","type":"journal-article","created":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T04:52:00Z","timestamp":1741755120000},"source":"Crossref","is-referenced-by-count":13,"title":["SH3GL1\u2010activated FTH1 inhibits ferroptosis and confers doxorubicin resistance in diffuse large B\u2010cell lymphoma"],"prefix":"10.1002","volume":"15","author":[{"given":"Zi\u2010Wen","family":"Duan","sequence":"first","affiliation":[{"name":"Department of Hematology the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital  Nanjing China"},{"name":"Key Laboratory of Hematology of Nanjing Medical University  Nanjing 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