Investigation of LARP1 regulated cellular pathways in acute myeloid leukemia

We demonstrate that LARP1, an RNA-binding protein regulated by mTOR and CDK9, promotes leukemic cell fitness and drug resistance in acute myeloid leukemia (AML). Using CRISPR/Cas9-mediated knockout models and multi-omics profiling, we show that LARP1 uniquely regulates the translation of transcripts involved in metabolism, cell cycle, and immune signalling, independent of mTOR or CDK9 inhibition. LARP1 loss reprograms mitochondrial and amino acid metabolism, downregulates cytidine deaminase, and enhances sensitivity to azacitidine and cytarabine. These findings establish LARP1 as a critical integrator of translational and metabolic control in AML and a potential therapeutic target.