Exploring the cytotoxic effects of dBET1 on multiple molecular subtypes of Acute myeloid leukemia cells

Acute myeloid leukemia (AML) represents an aggressive hematopoietic malignancy with a prognosis inferior to that of other leukemias. Recent targeted therapies offer new opportunities to achieve better treatment outcomes. However, due to the complex heterogeneity of AML, its prognosis is remain dismal. In this study, we first identified the correlation between high expression of BRD4 and overall survival of AML patients. Targeted degradation of BRD2, BRD3, and BRD4 proteins by dBET1, a PROTAC against BET family members, showed cytotoxic effects on Kasumi (AML1-ETO), NB4 (PML-RARa), THP-1 (MLL-AF9), and MV4-11 (MLL-AF4) AML cell lines representing different molecular subtypes of AML. Furthermore, we determined that dBET1 treatment arrested cell cycling and enhanced apoptosis and c-MYC as the downstream target. Collectively, our results indicated that dBET1 has broad cytotoxic effects on AML cells with different molecular lesions and provide more benefits to AML patients. Overall design: mRNA profiles of NB4 cells treated with 8 µM or same volume DMSO for 24 h were generated by RNA sequencing, in double, using Illumina NovaSeq6000.