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December 8, 2025Blood

XPO1 inhibition by selinexor blocks nucleo-cytoplasmic trafficking of multiple members of the NF-kb family in MPN cell lines and primary myelofibrosis cells

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Authors

APAnthony D. PomicterJMJames MarvinAEAndrea Ellero

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Overview

Imaging flow cytometry reveals selinexor impacts cytokines in myelofibrosis cells, suggesting therapeutic potential for ruxolitinib combination.

Key Points

  • The study assesses how selinexor affects nucleo-cytoplasmic trafficking of proteins in myelofibrosis cells.
  • Used imaging flow cytometry to evaluate protein localization changes in MPN cells after selinexor treatment.
  • Cells were exposed to selinexor and analyzed for alterations in NF-kB protein spatial distribution.
  • Fixed and stained myelofibrosis patient samples and HEL cell line to quantify nuclear and cytoplasmic localization of proteins.
  • Selinexor induced G0/G1 cell cycle arrest in HEL cells within 16 hours.
  • Nuclear localization of RELA increased from 39.4% to 93.2% after selinexor treatment.
  • IκBα levels in the nucleus rose from 33.1% to 85.1%, consistent with inhibition of NF-kB activity.

Cite This Study

Pomicter et al. (2025) studied this question.

synapsesocial.com/papers/69362f484fa91c937236d6a7https://doi.org/10.1182/blood-2025-7275
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Also Consider

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

  1. 1Selinexor alone and in combination with JAK inhibitors suppresses pro-inflammatory cytokine secretion from primary myelofibrosis cells ex vivo2025
  2. 2Targeting nuclear export and Janus Kinase/Signal Transducer and Activator of Transcription ( <scp>JAK</scp> / <scp>STAT)</scp> signalling in myelofibrosis: A novel combinatorial strategy that impacts intrinsic and microenvironment‐related pathways2026
  3. 3Phase 3 randomized double-blind study evaluating selinexor, an XPO1 inhibitor, plus ruxolitinib in JAKi-naïve myelofibrosis.2024 · 2 citations
  4. 4Phase 2 study evaluating selinexor monotherapy in patients with JAKi-naïve myelofibrosis and moderate thrombocytopenia.2024 · 1 citations
  5. 5Single‐Agent Selinexor Versus Physician's Choice in Previously Treated Myelofibrosis: Results From the Phase 2 XPORT‐035 Study2026