Related Experiment Video

Updated: Aug 12, 2025

Subcellular Fractionation of Primary Chronic Lymphocytic Leukemia Cells to Monitor Nuclear/Cytoplasmic Protein Trafficking
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Subcellular Fractionation of Primary Chronic Lymphocytic Leukemia Cells to Monitor Nuclear/Cytoplasmic Protein Trafficking

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Exportin 1-mediated nuclear/cytoplasmic trafficking controls drug sensitivity of classical Hodgkin's lymphoma

Mélody Caillot1, Hadjer Miloudi1, Antoine Taly2,3

  • 1Normandie Univ, INSERM, Unicaen, Caen, France.

Molecular Oncology
|February 2, 2023
PubMed

Insights

Mutations in Exportin 1 (XPO1) make lymphoma cells more sensitive to selinexor, a cancer drug. This XPO1 mutation may serve as a biomarker for predicting treatment response in certain B-cell lymphomas.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Exportin 1 (XPO1) is a key nuclear export receptor regulating protein trafficking and function.
  • XPO1 overexpression is common in various cancers.
  • Small molecule inhibitors of nuclear export (SINEs) target XPO1.

Purpose of the Study:

  • To investigate the functional impact of XPO1 mutations (XPO1E571K) in primary mediastinal B-cell lymphoma (PMBL) and classical Hodgkin's lymphoma (cHL).
  • To evaluate the response of PMBL and cHL cells with XPO1 mutations to selinexor (a SINE) and ibrutinib (a Bruton tyrosine kinase inhibitor).

Main Methods:

  • Studied the response of PMBL and cHL cells to selinexor and ibrutinib.
  • Analyzed the degradation rates of wild-type versus mutant XPO1.
  • Investigated the subcellular localization of p65 (RELA) and p52 (NFκB2) transcription factors.

Main Results:

  • XPO1 mutation leads to increased sensitivity to selinexor due to accelerated degradation of mutant XPO1.
  • Ibrutinib response is associated with altered trafficking of p65 and p52 transcription factors.
  • XPO1 mutation identified as a potential biomarker for SINEs and NFκB pathway-targeting drugs.

Conclusions:

  • XPO1 mutation influences lymphoma cell sensitivity to targeted therapies.
  • Aberrant nuclear-cytoplasmic trafficking of NFκB components contributes to drug response.
  • XPO1 mutation can serve as a predictive biomarker for treatment outcomes in B-cell hemopathies.
Keywords:
NFκB signalingibrutinibimportazoleimportin β1selinexor

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