BCLAF1 links RNA splicing to ATF4-dependent metabolic adaptation in acute myeloid leukemia.

BCLAF1 is required for productive splicing of ATF4 mRNA in acute myeloid leukemia, sustaining ATF4 protein levels and metabolic gene programs.

• Why it matters: Non-genetic mechanisms that help AML cells maintain survival are less defined than the mutational drivers, limiting therapeutic targeting beyond genetics.
• What they did: Using human AML cells and murine models, the study shows BCLAF1 associates with core spliceosome components and regulates alternative splicing, with BCLAF1 loss reducing ATF4 mRNA splicing and protein.
• The result: Reduced ATF4 after BCLAF1 loss impairs de novo amino acid biosynthesis and increases sensitivity to venetoclax, suggesting BCLAF1-linked splicing is a therapeutic vulnerability in AML.

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