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

Rinaldetti, S. ; Chepeleva, M. ; Hedblom, A. LU ; Sticht, C. ; Muciek, M. ; Panayiotidis, P. ; Richter, J. LU ; Olsson-Strömberg, U. ; Nowak, D. and Nowak, V. , et al. (2026) In Leukemia 40(8). p.1698-1707
Abstract

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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Leukemia
volume
40
issue
8
pages
10 pages
publisher
Nature Publishing Group
external identifiers
  • pmid:42315627
  • scopus:105042294389
ISSN
0887-6924
DOI
10.1038/s41375-026-03001-5
language
English
LU publication?
yes
id
ac864ab6-bf39-41dc-99d0-fabfb2b9d9ba
date added to LUP
2026-09-11 15:25:43
date last changed
2026-09-11 15:26:38
@article{ac864ab6-bf39-41dc-99d0-fabfb2b9d9ba,
  abstract     = {{<p>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.</p>}},
  author       = {{Rinaldetti, S. and Chepeleva, M. and Hedblom, A. and Sticht, C. and Muciek, M. and Panayiotidis, P. and Richter, J. and Olsson-Strömberg, U. and Nowak, D. and Nowak, V. and Ljungman, P. and von Bubnoff, N. and Lotfi, K. and Stenke, L. and Brümmendorf, T. H. and Hjorth-Hansen, H. and Gedde-Dahl, T. and Majeed, W. and Burchert, A. and Nazarov, P. V. and Felde, E. and Tarnopolscaia, I. and Hoelting, C. and Fabarius, A. and Hofmann, W. K. and Mahon, F. X. and Saussele, S. and Pfirrmann, M.}},
  issn         = {{0887-6924}},
  language     = {{eng}},
  number       = {{8}},
  pages        = {{1698--1707}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Leukemia}},
  title        = {{Comprehensive molecular characterization of treatment-free remission and molecular relapse in chronic myeloid leukemia patients : the EURO-SKI Biomarker Study}},
  url          = {{http://dx.doi.org/10.1038/s41375-026-03001-5}},
  doi          = {{10.1038/s41375-026-03001-5}},
  volume       = {{40}},
  year         = {{2026}},
}