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An Immune Dysfunction Signature Score Predicts Survival in MDS Patients: Insights From a Longitudinal, Multicenter

Yu-Hung Wang1,2,3, Carmelo Gurnari4,5, Valeria Visconte4

  • 1Division of Haematology, National Taiwan University Hospital, Taipei, Taiwan.

Cancer Science
|April 28, 2026
PubMed
Summary

An immune dysfunction signature (IDS) effectively predicts outcomes in myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML). This signature improves risk stratification and monitors disease progression, offering new therapeutic strategies for these myeloid neoplasms.

Keywords:
MDSimmune dysfunction signaturemulticenter studyprognostication

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Area of Science:

  • Hematology
  • Immunology
  • Oncology

Background:

  • Myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML) are clonal myeloid neoplasms.
  • Genetic mutations and immune dysregulation drive disease progression and poor patient outcomes.
  • Current prognostic systems (IPSS-R, IPSS-M) do not account for immune system alterations.

Purpose of the Study:

  • To evaluate the biological and clinical significance of an immune dysfunction signature (IDS) in MDS and CMML.
  • To determine if IDS can improve existing prognostic models and track disease evolution.
  • To identify potential therapeutic targets for IDS-high patients.

Main Methods:

  • Transcriptomic data from multi-center MDS and CMML cohorts were analyzed to derive IDS scores.
  • Multivariable analyses were performed to assess IDS prognostic value alongside established markers (IPSS-R, IPSS-M, TP53).
  • Longitudinal IDS changes were correlated with disease progression, remission, and acute transformation. Drug response signatures were integrated to identify therapeutic vulnerabilities.

Main Results:

  • Elevated IDS scores were significantly associated with worse leukemia-free and overall survival in both MDS and CMML.
  • IDS provided independent prognostic value, enhancing the accuracy of existing risk stratification models.
  • Rising IDS correlated with disease progression and acute transformation, while declining IDS indicated remission. IDS-high cases showed potential sensitivity to multikinase and NF-κB inhibitors.

Conclusions:

  • The immune dysfunction signature (IDS) is a validated, dynamic biomarker for MDS and CMML.
  • IDS refines risk stratification, enables longitudinal disease monitoring, and guides personalized immunotherapy strategies.
  • Targeting immune dysfunction presents a promising therapeutic avenue for patients with MDS and CMML.