Menin-MLL inhibitors enhance JUND activity in MLLr leukemic cells, contributing to tumorigenesis and therapy resistance.

Menin-MLL inhibitors increase JUND activity in MLL-rearranged leukemic cells, contributing to tumor growth and therapy resistance.

• Why it matters: Understanding how menin-MLL inhibitors affect other protein interactions is crucial for improving leukemia treatments, especially since resistance mechanisms limit their effectiveness.
• What they did: The study used mass spectrometry, CRISPR gene editing, and chromatin assays to show that menin-MLL inhibitors also disrupt menin-JUND interactions and increase JUND's binding to DNA, promoting gene activation.
• The result: Elevated JUND activity reduces the effectiveness of menin-MLL inhibitors, but combining JUND or JNK inhibitors with these drugs enhances anti-leukemic effects and decreases tumor burden in mice.