BCR-ABL1 kinase regulates the activation of RAC guanosine triphosphatases (RAC GTPases). In CML progenitors, RAC GTPases include RAC1, RAC2, and RAC3, which integrate signal chemokines, growth factors, and adhesion receptors to coordinate cell responses. BCR-ABL1 activates a variety of effectors to promote cell proliferation, including RAC GTPases. In turn, RAC GTPases may mediate STAT5 phosphorylation. Inhibition of RAC GTPases by the specific RAC inhibitor NSC23766 abrogates BCR-ABL1–induced cell proliferation. GDP, guanosine diphosphate; GTP, guanosine triphosphate.