TARGETING THE EPIGENETIC MECHANISM IN ACUTE MYELOID LEUKAEMIA

Abstract

TARGET THERAPY HAS ALWAYS BEEN THE FOCUS OF STUDIES OF THERAPEUTIC APPROACHES IN CANCER, ESPECIALLY IN TREATMENT OF AML. ANEW SMALL MOLECULAR DRUG, JQ1, TARGETING THE EPIGENETIC READER BRD4, HAS BEEN SHOWN TO INDUCE CELL CYCLE ARREST IN DIFFERENT CANCERS THROUGH INHIBITING THE WELL-KNOWN ONCOGENE, MYC. HOWEVER, OTHER MECHANISMS OF JQ1 HAVE NOT BEEN WELL STUDIED IN AML. IN THIS STUDY, I FOUND THAT JQ1 IS ABLE TO INDUCE CELL DEATH IN AML CELLS THROUGH REACTIVATING A TUMOR SUPPRESSOR, TXNIP, INDUCING APOPTOSIS THROUGH THE ASK1-MAPK PATHWAY. FURTHER STUDIES CONFIRMED THAT MYC COULD REPRESS THE EXPRESSION OF TXNIP THROUGH MIR-17-92 CLUSTER. THESE FINDINGS ENHANCED OUR UNDERSTANDING OF THE DETAILED MECHANISM OF JQ1-INDUCED APOPTOSIS IN AML, DEMONSTRATED THE REPRESSIVE ROLE OF MYC ON SPECIFIC GENE EXPRESSION, AND PROVIDED VALUABLE DATA IN OUR FIGHTING AGAINST AML.