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The molecular mechanisms underlying sustained treatment-free remission (TFR) and loss of TFR, are still poorly understood. To address this, we performed whole transcriptome gene expression analyses coupled with NanoString nCounter-based absolute gene quantification. Gene expression was assessed in peripheral blood leukocytes from 240 CML patients on the final day of TKI intake (training sample:\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009122, validation sample:\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009118) as well as from 10 healthy controls. To identify TKI-specific mechanisms, transcriptomic data from an external dataset of 96 TKI-na\u00efve CML patients was incorporated into our analyses. TFR patients showed an activation of GATA1, KLF1 and MYBL1 regulons characteristic for erythroid progenitor cells. TFR patients maintain persistent communication between innate (natural killer and dendritic cells) and adaptive immunity (e.g., CD8+, CD4+, and \u03b3\u03b4 T lymphocytes), mirroring patterns observed in healthy controls. This intercellular communication is disrupted in patients with loss of TFR. Furthermore, we identified an FLT3 threshold that distinguished two patient groups with significantly different probabilities of TFR loss. Leveraging mechanisms that reestablish or reinforce the communication between innate and adaptive immunity could be pivotal in achieving durable TFR.\n                  <\/jats:p>","DOI":"10.1038\/s41375-026-03001-5","type":"journal-article","created":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T09:36:52Z","timestamp":1781775412000},"page":"1698-1707","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Comprehensive molecular characterization of treatment-free remission and molecular relapse in chronic myeloid leukemia patients: the EURO-SKI Biomarker Study"],"prefix":"10.1038","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1053-3831","authenticated-orcid":false,"given":"S.","family":"Rinaldetti","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3036-4916","authenticated-orcid":false,"given":"M.","family":"Chepeleva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Hedblom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3596-6094","authenticated-orcid":false,"given":"C.","family":"Sticht","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Muciek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Panayiotidis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0374-6823","authenticated-orcid":false,"given":"J.","family":"Richter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"U.","family":"Olsson-Str\u00f6mberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7130-7921","authenticated-orcid":false,"given":"D.","family":"Nowak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V.","family":"Nowak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8281-3245","authenticated-orcid":false,"given":"P.","family":"Ljungman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"von Bubnoff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5797-7232","authenticated-orcid":false,"given":"K.","family":"Lotfi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Stenke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9677-3723","authenticated-orcid":false,"given":"T. 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