{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T07:04:28Z","timestamp":1792047868646,"version":"4.4.0"},"reference-count":35,"publisher":"American Society for Clinical Investigation","issue":"20","license":[{"start":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:00:00Z","timestamp":1792022400000},"content-version":"vor","delay-in-days":44,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China","award":["82270236,82341080,82273217,82400271,82403710"],"award-info":[{"award-number":["82270236,82341080,82273217,82400271,82403710"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Tianjin Municipal Natural Science Foundation of China","award":["22JCJQJC00090"],"award-info":[{"award-number":["22JCJQJC00090"]}]},{"name":"China Foundation For Youth Entrepreneurship and Employment-Incaier Public Welfare Fund","award":["HH25KYHX0016,HH25KYHX0010"],"award-info":[{"award-number":["HH25KYHX0016,HH25KYHX0010"]}]},{"name":"Haihe Laboratory of Cell Ecosystem Innovation Fund","award":["25HHXBSS00001"],"award-info":[{"award-number":["25HHXBSS00001"]}]},{"name":"Sichuan Science and Technology Program","award":["2025ZNSFSC0737"],"award-info":[{"award-number":["2025ZNSFSC0737"]}]},{"name":"Chinese Academy of Medical Science (CAMS) Innovation Fund for Medical Sciences","award":["2023-I2M-3-014,2023-I2M-2-007,2025-I2M-XHJC-037,2025-I2M-XHXX-135,2025-I2M-XHXX-134,2025-I2M-TS-07"],"award-info":[{"award-number":["2023-I2M-3-014,2023-I2M-2-007,2025-I2M-XHJC-037,2025-I2M-XHXX-135,2025-I2M-XHXX-134,2025-I2M-TS-07"]}],"id":[{"id":"https:\/\/ror.org\/02drdmm93","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Tianjin Municipal Science and Technology Commission Grant","award":["25ZXRKSY00050"],"award-info":[{"award-number":["25ZXRKSY00050"]}],"id":[{"id":"https:\/\/ror.org\/03wb1xh22","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,15]]},"abstract":"<jats:p>\n                    Activating mutations in FMS-like tyrosine kinase 3 (FLT3) drive aggressive acute myeloid leukemia (AML) and confer poor prognosis. Although FLT3 inhibitors have improved AML outcomes, their efficacy is frequently limited by microenvironment-mediated signaling and treatment-emergent resistance. XY0206 is a structurally optimized derivative of sunitinib, an inhibitor approved for multiple solid tumors. Biochemical, multi-omics, and functional analyses showed that XY0206 directly engages FLT3 and suppresses downstream STAT5, AKT, and ERK signaling, resulting in apoptosis of AML cells with\n                    <jats:italic>FLT3<\/jats:italic>\n                    \u2013internal tandem duplications (\n                    <jats:italic>FLT3<\/jats:italic>\n                    -ITD). Across models of FLT3-dependent resistance, XY0206 retained antileukemic activity, including in\n                    <jats:italic>FLT3<\/jats:italic>\n                    -ITD cells harboring the F691L gatekeeper mutation, a recurrent alteration conferring resistance to approved FLT3 inhibitors. In primary AML blasts and xenograft models, XY0206 exhibited enhanced antileukemic activity with favorable tolerability relative to gilteritinib. In a phase I\/II trial of XY0206 monotherapy in patients with relapsed or refractory (R\/R) AML (ClinicalTrials.gov identifier NCT04471064), XY0206 achieved a composite complete remission rate (CRc) of 45.7% overall, with a notable 60.0% CRc rate among patients with\n                    <jats:italic>FLT3<\/jats:italic>\n                    -ITD mutations. Three of 8 patients with prior FLT3 inhibitor\u2013exposed R\/R AML also achieved CRc. Together, these findings support further clinical evaluation of XY0206 as an FLT3-directed therapeutic in AML, particularly in disease settings with reduced sensitivity to existing FLT3 inhibitors.\n                  <\/jats:p>","DOI":"10.1172\/jci204701","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T16:02:32Z","timestamp":1788278552000},"source":"Crossref","is-referenced-by-count":1,"title":["XY0206 targets FLT3-dependent resistance states in acute myeloid leukemia"],"prefix":"10.1172","volume":"136","author":[{"given":"Long","family":"Shen","sequence":"first","affiliation":[{"name":"State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China."},{"name":"Tianjin Institutes of Health Science, Tianjin, 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