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Comprehensive molecular characterization of treatment-free remission and molecular relapse in chronic myeloid leukemia patients: the EURO-SKI Biomarker Study

The European Stop Kinase Inhibitors (EURO-SKI) trial was launched to investigate the discontinuation of tyrosine kinase inhibitors (TKIs) in patients with chronic myeloid leukemia (CML). The molecular mechanisms underlying sustained treatment-free remission (TFR) and loss of TFR, are still poorly un...

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Main Authors: Rinaldetti, Sébastien (Author) , Chepeleva, M. (Author) , Hedblom, A. (Author) , Sticht, Carsten (Author) , Muciek, Maria (Author) , Panayiotidis, P. (Author) , Richter, J. (Author) , Olsson-Strömberg, U. (Author) , Nowak, Daniel (Author) , Nowak, Verena (Author) , Ljungman, P. (Author) , von Bubnoff, N. (Author) , Lotfi, K. (Author) , Stenke, L. (Author) , Brümmendorf, T. H. (Author) , Hjorth-Hansen, H. (Author) , Gedde-Dahl, T. (Author) , Majeed, W. (Author) , Burchert, A. (Author) , Nazarov, P. V. (Author) , Felde, Elena (Author) , Tarnopolscaia, Irina (Author) , Hoelting, Carolin (Author) , Fabarius, Alice (Author) , Hofmann, Wolf-Karsten (Author) , Mahon, F.-X. (Author) , Saußele, Susanne (Author) , Pfirrmann, M. (Author)
Format: Article (Journal)
Language:English
Published: 18 June 2026
In: Leukemia
Year: 2026, Pages: 1-10
ISSN:1476-5551
DOI:10.1038/s41375-026-03001-5
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1038/s41375-026-03001-5
Verlag, kostenfrei, Volltext: https://www.nature.com/articles/s41375-026-03001-5
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Author Notes:S. Rinaldetti, M. Chepeleva, A. Hedblom, C. Sticht, M. Muciek, P. Panayiotidis, J. Richter, U. Olsson-Strömberg, D. Nowak, V. Nowak, P. Ljungman, N. von Bubnoff, K. Lotfi, L. Stenke, T.H. Brümmendorf, H. Hjorth-Hansen, T. Gedde-Dahl, W. Majeed, A. Burchert, P.V. Nazarov, E. Felde, I. Tarnopolscaia, C. Hoelting, A. Fabarius, W.-K. Hofmann, F.-X. Mahon, S. Saussele and M. Pfirrmann
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Summary:The European Stop Kinase Inhibitors (EURO-SKI) trial was launched to investigate the discontinuation of tyrosine kinase inhibitors (TKIs) in patients with chronic myeloid leukemia (CML). 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 = 122, validation sample: n = 118) as well as from 10 healthy controls. To identify TKI-specific mechanisms, transcriptomic data from an external dataset of 96 TKI-naïve 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 γδ 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.
Item Description:Gesehen am 16.07.2026
Physical Description:Online Resource
ISSN:1476-5551
DOI:10.1038/s41375-026-03001-5

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