Epigenetic reactivation of the tumor suppressor ZBTB7A by KDM4 inhibition in human acute myeloid leukemia - PubMed
3 hours ago
- #Epigenetics
- #AML
- #Tumor Suppressor
- ZBTB7A is identified as a tumor suppressor gene (TSG) down-regulated in AML, associated with poor survival outcomes.
- Loss of ZBTB7A amplifies TNF signaling, leading to a dysfunctional inflammatory state that accelerates AML progression.
- ZFP36L2 binds to the 3'UTR of ZBTB7A, promoting its transcript degradation in human AML cells.
- A CRISPR-based screening approach identified KDM4 histone demethylases as a therapeutic target to restore ZBTB7A function.
- Pharmacologic inhibition of KDM4 up-regulates ZBTB7A, promotes terminal differentiation, and shows broad antileukemic efficacy across AML subtypes while preserving normal hematopoiesis.
- Epigenetic therapy targeting KDM4 is a promising strategy to reactivate ZBTB7A's tumor suppressor function in hematologic cancers.