Researchers have uncovered a crucial enzyme responsible for a specific chemical modification linked to the growth of a severe subtype of acute myeloid leukemia (AML), offering fresh insights for potential targeted therapies.
The study focused on mixed-lineage leukemia-rearranged (MLL-r) AML, a form of blood cancer marked by high levels of a histone modification called H3K4me3. Histones help regulate gene activity, and their modification can affect cancer cell behaviour. Until now, the enzymes driving this high H3K4me3 in MLL-r AML and their impact on cancer progression were unclear.
Using a CRISPR-based screening technique, scientists identified the enzyme SETD1B as essential for maintaining H3K4me3 levels and supporting the growth of AML cells with mutations in FLT3 or Nras genes. Disrupting SETD1B’s catalytic region led to reduced cancer cell proliferation and lowered activity in the MYC gene pathway, which is known to promote tumour growth.
Interestingly, restoring MYC expression or inhibiting a related demethylase enzyme could reverse the growth defects caused by SETD1B loss, highlighting SETD1B’s role in regulating gene expression through H3K4me3 modification.
These findings suggest that targeting SETD1B or its downstream effects may provide new treatment strategies for MYC-dependent leukemia. The research offers a promising avenue for developing biomarkers and therapies aimed at aggressive AML subtypes, potentially improving outcomes for patients with this challenging disease.
Reference
Izumi S et al. Regulation of H3K4me3 breadth and MYC expression by the SETD1B catalytic domain in MLL-rearranged leukemia. Leukemia. 2025;39:1627-39.
