Resumen
This study investigates the combined therapeutic potential of revumenib and tamibarotene in acute myeloid leukemia (AML) with histone-lysine-N-methyltransferase 2A rearrangement (KMT2Ar) or mutated Nucleophosmin gene (NPM1c). Menin inhibition is considered a promising treatment for such AML cases, but resistance mutations pose challenges. Elevated retinoic acid receptor alpha (RARA) expression levels indicate favorable outcomes with tamibarotene, known for restoring differentiation or inducing apoptosis. The combination of revumenib and tamibarotene demonstrated highly synergistic effects in MV4:11 cells, marked by apoptosis induction while MOLM13 and OCI-AML3 cells showed increased differentiation markers. Patient-derived AML cells exhibited in parts corresponding effects, suggesting a potential strategy for relapsed/refractory AML patients with specific molecular characteristics.