We reveal a FOXO3a-mediated transcriptional control of FOXM1 expression, a crucial function of FOXM1 with respect to TKI resistance and disease progression, using a conditional Foxm1fl/fl knockout mouse model as well as pharmacological inhibition of FOXM1 in patient-derived pre-B ALL cells. The gene discussed is FOXM1; the disease is acute lymphoblastic leukemia.