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December 8, 2025BloodOpen Access

SRSF2 mutation induces BH3 mimetics sensitivity via BCL2L2 mis-splicing

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Authors

TMTakumi MatsushimaKAKoichi Akashi

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Overview

Experiments show SRSF2 mutations enhance venetoclax and MCL1 sensitivity in AML, indicating altered apoptosis regulation due to splicing changes.

Key Points

  • To elucidate the mechanisms by which SRSF2 mutations affect drug sensitivity in acute myeloid leukemia (AML).
  • Generated isogenic human AML cell lines with SRSF2 mutation via lentiviral transduction.
  • Analyzed drug sensitivity to venetoclax and MCL1 inhibitor in these cell lines.
  • Conducted RNA sequencing and RT-PCR for gene expression analysis.
  • SRSF2-mutant AML cells showed increased sensitivity to venetoclax compared to wild-type.
  • BCL2L2 downregulation due to aberrant splicing was observed in SRSF2-mutant cells.
  • Restoration of BCL2L2 reversed sensitivity to BH3 mimetics.

Cite This Study

Matsushima et al. (2025) studied this question.

synapsesocial.com/papers/69362f4e4fa91c937236d890https://doi.org/10.1182/blood-2025-5158
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Also Consider

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  1. 1Sensitivity to ATR-CHK1 pathway inhibition in AML/MDS is enhanced by SRSF2 mutations and reduced by RUNX1 loss2025
  2. 2Poor Prognosis of SRSF2 Gene Mutations in Patients Treated with VEN-AZA for Newly Diagnosed Acute Myeloid Leukemia2024 · 6 citations
  3. 3The Study of SRSF1 Regulates Abnormal Alternative Splicing of <i>BCL2L11</i> and the Role in Refractory Acute Myeloid Leukemia2024 · 1 citations
  4. 4SRSF2 mutations contribute to bone marrow immune microenvironment alterations2026
  5. 5Identification and functional characterization of splicing factors implicated in mantle cell lymphoma aggressiveness2025 · 1 citations