Inhibition of the RacGEF VAV3 by the Small Molecule IODVA1 Impedes RAC Signaling and Overcomes Resistance to Tyrosine Kinase Inhibition in Acute Lymphoblastic Leukemia

Researchers used cellular, mouse, and humanized models of RAC-dependent BCR-ABL1-driven and Ph-like acute lymphoblastic leukemia to identify VAV3, a tyrosine phosphorylation–dependent RAC guanine nucleotide exchange factor (RacGEF), as the target of the small molecule IODVA1.