A study published in Nature identifies Brd4 as a critical therapeutic target in acute myeloid leukemia (AML). Using a non-biased RNA interference (RNAi) screen targeting chromatin regulators in an AML mouse model, researchers found that Brd4 is essential for maintaining AML. Suppression of Brd4 using small hairpin RNAs (shRNAs) or the small-molecule inhibitor JQ1 led to significant antileukaemic effects, including terminal myeloid differentiation and elimination of leukemia stem cells. Similar results were observed in various human AML cell lines and primary patient samples, indicating broad activity of JQ1 across AML subtypes. The effects of Brd4 suppression were partly due to its role in sustaining Myc expression, suggesting that JQ1 could be a means to suppress MYC in cancer. The study demonstrates that small-molecule inhibition of Brd4 is a promising therapeutic strategy for AML and potentially other cancers, highlighting the value of RNAi screening in identifying epigenetic vulnerabilities for pharmacological intervention.A study published in Nature identifies Brd4 as a critical therapeutic target in acute myeloid leukemia (AML). Using a non-biased RNA interference (RNAi) screen targeting chromatin regulators in an AML mouse model, researchers found that Brd4 is essential for maintaining AML. Suppression of Brd4 using small hairpin RNAs (shRNAs) or the small-molecule inhibitor JQ1 led to significant antileukaemic effects, including terminal myeloid differentiation and elimination of leukemia stem cells. Similar results were observed in various human AML cell lines and primary patient samples, indicating broad activity of JQ1 across AML subtypes. The effects of Brd4 suppression were partly due to its role in sustaining Myc expression, suggesting that JQ1 could be a means to suppress MYC in cancer. The study demonstrates that small-molecule inhibition of Brd4 is a promising therapeutic strategy for AML and potentially other cancers, highlighting the value of RNAi screening in identifying epigenetic vulnerabilities for pharmacological intervention.