{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T12:27:31Z","timestamp":1793795251719,"version":"4.6.1"},"reference-count":30,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T00:00:00Z","timestamp":1781481600000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["HemaSphere"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Lenalidomide (Len) is the standard of care for red blood cell transfusion\u2010dependent (TD) patients with myelodysplastic syndromes (MDS) and del(5q). A Phase III clinical trial (SintraRev) demonstrated better efficacy of early treatment with Len in anemic del(5q) MDS patients prior to TD, but clonal evolution with this approach remained unexplored. We evaluated changes in mutational profiles of non\u2010TD del(5q) MDS patients treated with Len to assess whether early administration of Len could reduce or worsen the mutational burden in those patients. The molecular profile of patients included in the SintraRev trial was analyzed by targeted sequencing. Median follow up of patients was 60.6 months (interquartile range [IQR] 32.3\u201373.9). Next\u2010generation sequencing (NGS) was available in a total of 51 patients.\n                    <jats:italic>SF3B1<\/jats:italic>\n                    (25.5%) and\n                    <jats:italic>TP53<\/jats:italic>\n                    (21.3%) were the most frequently mutated genes. Clonal evolution during treatment among patients receiving Len or placebo (Pcb) was markedly different, with a 41.2% reduction in predominating clones in the Len arm, while remaining stable\/increase in 100% of Pcb patients after 2 years. Mutations in\n                    <jats:italic>SF3B1<\/jats:italic>\n                    and\n                    <jats:italic>TP53<\/jats:italic>\n                    decreased\/remained stable in the Len cohort, while only\n                    <jats:italic>DNMT3A<\/jats:italic>\n                    mutations increased under cytogenetic response. Regarding disease progression, only 20% of Len patients carrying\n                    <jats:italic>TP53<\/jats:italic>\n                    mutations developed acute myeloid leukemia (AML), similar to the Pcb group (20%). Treatment with low\u2010dose Len in transfusion\u2010independent del(5q) MDS reduced the mutational burden of most genes and did not promote the expansion of preexisting clones or AML progression, especially\n                    <jats:italic>TP53<\/jats:italic>\n                    \u2010mutated clones. Early administration of Len in del(5q) MDS patients without TD may be an effective therapeutic approach with a manageable safety profile regarding clonal evolution.\n                  <\/jats:p>","DOI":"10.1002\/hem3.70402","type":"journal-article","created":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T09:25:20Z","timestamp":1781515520000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Mutational dynamics in patients with del(5q) MDS treated with lenalidomide prior to transfusion dependency\u2014Molecular results from the Sintrarev clinical trial"],"prefix":"10.1002","volume":"10","author":[{"given":"Sof\u00eda","family":"Toribio Castell\u00f3","sequence":"first","affiliation":[{"name":"Molecular Genetics in Oncohematology Institute of Biomedical Research of Salamanca (IBSAL) \u2010 Cancer Research Center of Salamanca (USAL\u2010CSIC) Salamanca Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix","family":"L\u00f3pez\u2010Cadenas","sequence":"additional","affiliation":[{"name":"Hematology Department, University Hospital of Salamanca Institute of Biomedical Research of Salamanca (IBSAL) Salamanca Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claude","family":"Preudhomme","sequence":"additional","affiliation":[{"name":"Laboratory of Hematology Lille University Hospital Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Molecular Genetics in Oncohematology Institute of Biomedical Research of Salamanca (IBSAL) \u2010 Cancer Research Center of Salamanca (USAL\u2010CSIC) Salamanca Spain"},{"name":"Hematology Department, University Hospital of Salamanca Institute of Biomedical Research of Salamanca (IBSAL) Salamanca 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Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aline","family":"Renneville","sequence":"additional","affiliation":[{"name":"Laboratory of Hematology Lille University Hospital Lille France"},{"name":"Biology and Pathology Department and INSERM U1287 Gustave Roussy Villejuif France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joaqu\u00edn","family":"S\u00e1nchez\u2010Garcia","sequence":"additional","affiliation":[{"name":"IMIBIC, Hematology University Hospital Reina Sof\u00eda, UCO C\u00f3rdoba Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa","family":"Coll","sequence":"additional","affiliation":[{"name":"Hospital Josep Trueta \u2010 ICO Girona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bohrane","family":"Slama","sequence":"additional","affiliation":[{"name":"CH Avignon Avignon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 \u00c1ngel","family":"Hern\u00e1ndez\u2010Rivas","sequence":"additional","affiliation":[{"name":"Hematology Department, Hospital Universitario Infanta Leonor Universidad Complutense Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvain","family":"Thepot","sequence":"additional","affiliation":[{"name":"Service des maladies du sang CHU d'Angers and FHU GOAL Angers France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Bernal","sequence":"additional","affiliation":[{"name":"Hospital Universitario Central de Asturias, Instituto Universitario del Principado de Asturias (ISPA) Instituto Universitario de Oncolog\u00eda del Principado de Asturias (IUOPA) Oviedo Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agn\u00e8s","family":"Guerci\u2010Bresler","sequence":"additional","affiliation":[{"name":"Service d'H\u00e9matologie Centre Hospitalier Universtaire Brabois Vandoeuvre\u2010l\u00e8s\u2010Nancy France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ra\u00fal","family":"Azibeiro","sequence":"additional","affiliation":[{"name":"Hematology Department, University Hospital of Salamanca Institute of Biomedical Research of Salamanca (IBSAL) Salamanca Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Del Rey","sequence":"additional","affiliation":[{"name":"Molecular Genetics in Oncohematology Institute of Biomedical Research of Salamanca (IBSAL) \u2010 Cancer Research Center of Salamanca (USAL\u2010CSIC) Salamanca Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina S.","family":"G\u00f6tze","sequence":"additional","affiliation":[{"name":"Department of Medicine III, Hematology\/Oncology and Bavarian Center for Cancer Research (BZKF) Technical University of Munich School of Medicine and Health  Munich 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