RNA profiling of BCLAF1 knock-down MOLM-13 cell line

While the mutational landscape of AML is well characterized, the non-genetic processes that sustain leukemic maintenance remain comparatively less understood. Using murine models of AML and human AML cell lines, we identify BCL2-associated transcription factor 1 (BCLAF1) as a critical regulator of leukemic progression through control of mRNA processing.

BCLAF1 physically associates with core spliceosome components and regulates alternative splicing, with a predominant effect on intron retention. We demonstrate that BCLAF1 is required for the productive splicing of activating transcription factor 4 (ATF4) mRNA, thereby sustaining ATF4 protein expression. Loss of BCLAF1 reduces ATF4 protein levels, leading to downregulation of amino acid metabolic target genes essential for leukemic cell survival.