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Several acute myeloid leukemia genetic sub-types converge on high expression of HOX genes, critical for their self-renewal. A new orally bioavailable Menin-MLL inhibitor (VTP-50469) appears to promote their differentiation through direct effects on the HOX cofactor MEIS1, paving the way for clinical trials. Chemotherapy remains the main treatment option for patients with several tumor types. In this issue of Cancer Cell, Salvador-Barbero et al. demonstrate that treatment with CDK4/6 inhibitors after application of taxanes (or other chemot