Figure 3.
Sequential dual effects of ATRA therapy in patients with AML. (A) Selection of RARA mutations conferring ATRA resistance in ATRA-treated pediatric AML,102 fs, frameshift. (B) Proposed mechanism for ATRA activity and mutant selection in ATRA-treated AML. Treatment-selected dominant-negative RARA mutants (RARAMut) enhance self-renewal and block differentiation, contributing to AML relapses. CHEMO, anthracycline-based chemotherapy; LBD, ligand-binding domain; DBD, DNA-binding domain.