Not surprisingly, patients with TP53 mutations have vastly inferior responses to VEN-based therapies [13–16], supported by a recent pre-clinical study demonstrating that TP53 mutations confer resistance to HMA/VEN in vitro and in vivo [17] and CRISPR genome editing analyses demonstrating that the loss of p53-regulated apoptosis networks confers resistance of AML cells to VEN [18]. The gene discussed is TP53; the disease is acute myeloid leukemia.