G3BP1::CSF1R: a new and actionable gene fusion in acute megakaryoblastic leukemia

Here we report a novel targetable G3BP1::CSF1R fusion in acute megakaryoblastic leukemia. The fusion promotes cytokine-independent growth, leukemic engraftment and megakaryocytic commitment by repressing Kruppel-like factor 1. Disruption of juxta-membrane domain aggravates CSF1R kinase activity and dictates the leukemia phenotype. Overall design: To explore the mechanisms underlying GC-driven megakaryocytic commitment, RNA-seq was performed in M07E and TF1 cells transduced with EV, GC or GC543 lentivirus for 72 hours, with biological duplicates for each condition.