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December 8, 2025BloodOpen Access

Advanced myelofibrosis is marked by loss of NKG2D and DNAM-1 NK activating signaling and increased TIM-3 T CD8 exhaustion

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Authors

MMMariana MedeirosCGCamila GarcíaBABeatriz Adjafre

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Overview

Immunophenotyping shows immune dysfunction and altered NK and T cell profiles in myelofibrosis, indicating targets for immunomodulatory therapies.

Key Points

  • To investigate immune dysfunction in myelofibrosis using immunophenotyping of NK and T cells.
  • Analyzed peripheral blood mononuclear cells from untreated myelofibrosis patients and healthy donors.
  • Performed immunophenotyping to assess NK and T cell frequencies, maturation, and activation/inhibitory receptor expression.
  • Established a chimeric murine model of JAK2V617F-driven myeloproliferative neoplasm to explore immune alterations.
  • Myelofibrosis patients displayed increased total NK cells but reduced cytotoxic NK cell subtypes.
  • Marked decreases in NKG2D and DNAM-1 expression on NK cells were observed, alongside impaired T cell maturation.
  • The murine model revealed reduced frequencies of mature NK and CD3+ T cells, linked to chronic inflammation and immune exhaustion.

Cite This Study

Medeiros et al. (2025) studied this question.

synapsesocial.com/papers/69362f604fa91c937236dd5chttps://doi.org/10.1182/blood-2025-1980
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Broad Next-Generation Integrated Sequencing of Myelofibrosis Identifies Disease-Specific and Age-Related Genomic Alterations2024 · 11 citations
  2. 2Transcriptomic analysis of CD34⁺ cells in myelofibrosis highlights their role in extracellular matrix dysregulation and marrow fibrosis2025 · 1 citations
  3. 3Immunomodulatory role of megakaryocytes in the hematopoietic niche of myeloproliferative neoplasms2026 · 1 citations
  4. 4Data from Broad Next-Generation Integrated Sequencing of Myelofibrosis Identifies Disease-Specific and Age-Related Genomic Alterations2024
  5. 5Inflammatory and Immune Microenvironment in Myeloproliferative Neoplasms: Pathogenic Mechanisms and Therapeutic Opportunities2026