Synapse
⌘+K
Synapse
PulseExploreClubsResearchersJournals
Instagram
HomeClubsExplore
June 20, 2026Human GenomicsOpen Access

Variant-specific SF3B1 mutations drive distinct splicing and mitochondrial dysfunction in myelodysplastic neoplasms

View Full Paper
Ask AI
Bookmark
Share

Authors

AHAndrea HruštincováITIva TrsováDKDávid Kundrát

Discussion

Loading...

Member takes

Overview

Randomized trial investigates SF3B1 mutations' impact on splicing and mitochondrial function in MDS, highlighting therapeutic targets.

Key Points

  • This research aims to understand the clinical and functional impact of different SF3B1 mutations in myelodysplastic neoplasms (MDS).
  • Analyzed clinical data from 121 SF3B1-mutated MDS patients.
  • Conducted RNA sequencing on CD34⁺ patient bone marrow cells and CRISPR-engineered cell lines with specific SF3B1 variants.
  • Performed comprehensive analysis of splicing, gene expression, and mitochondrial bioenergetic parameters.
  • K666 variant was linked to shorter progression-free survival, distinct splicing abnormalities, and higher retained intron frequency compared to K700E.
  • Mitochondrial genes were frequently mis-spliced in K666-variant cells, with significant alterations in their expression levels.
  • Observed reduced complex IV activity and marked oxidative phosphorylation (OXPHOS) impairment in isogenic models, especially in K666N.

Cite This Study

Hruštincová et al. (2026) studied this question.

synapsesocial.com/papers/6a362e91db0793dc1a5363f1https://doi.org/10.1186/s40246-026-01000-2
View Full Paper
Ask AI
Bookmark
Share

Also Consider

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

  1. 1Clinical characteristics and molecular profiling of SF3B1-mutated myelodysplastic syndrome (MDS) in a real-world practice2025
  2. 2SF3B1 mutations K700E, K666N, and R625H: Gene expression and aberrant splicing consequences2025
  3. 3Impact of different Sf3b1 mutations on hematopoietic function and erythropoiesis2025
  4. 4MDS-associated SF3B1 mutations promote aberrant fate choice of hematopoietic stem cell via mis-splicing of mediator kinase module component CDK82025
  5. 5Clinical outcomes in spliceosome-mutant myelodysplastic neoplasms and Acute Myeloid Leukemia2025