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December 8, 2025Blood

Disrupting a new NFkB-IL-6-JAK2-STAT cascade with novel NFkB inhibitors reduces primary myelofibrosis growth

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Authors

NGNaseema GangatNSNa ShenWTWilliam Ka Fai Tse

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Overview

Research reveals disruption of NFkB-IL-6-JAK2-STAT axis reduces primary myelofibrosis growth through novel therapies Ixazomib and emetine.

Key Points

  • The aim is to explore JAKi resistance mechanisms and the therapeutic potential of NFkB inhibitors in primary myelofibrosis.
  • Created ruxolitinib-resistant HEL cells and examined NFkB/JAK2/STAT signaling via Western blot.
  • Identified biomarkers in PMF patients treated with BMS-9115437 using Western blot.
  • Conducted transcriptomic analysis and gene set enrichment for MPN patients' samples.
  • In vitro tests with shRNA, Ixazomib, or emetine to evaluate NFkB inactivation and cell growth.
  • Assessed tumor formation and biological mechanisms in HEL-engrafted mice.
  • JAKi exposure altered JAK2 phosphorylation patterns in resistant HEL cells, indicating persistent signaling.
  • Transcriptomic analysis revealed higher NFκB activity in PMF compared to other MPN subtypes.
  • Ixazomib significantly decreased tumor volume and weight in vivo, demonstrating its therapeutic potential.
  • In vitro, NFκB inhibition reduced proliferation and improved apoptosis markers in PMF cells.

Cite This Study

Gangat et al. (2025) studied this question.

synapsesocial.com/papers/69362f604fa91c937236dd62https://doi.org/10.1182/blood-2025-1990
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  1. 1<i>miR‐146a<sup>−/−</sup></i> mice model reveals that <scp>NF‐κB</scp> inhibition reverts <scp>inflammation‐driven</scp> myelofibrosis‐like phenotype2024 · 9 citations
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  3. 3FRACTION: protocol of a phase II study of Fedratinib and Nivolumab combination in patients with myelofibrosis and resistance or suboptimal response to JAK-inhibitor treatment of the German MPN study group (GSG-MPN)2024 · 15 citations
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