Exploring the cytotoxic effects of MZ1 on multiple molecular subtypes of B-cell acute lymphoblastic leukemia cells

Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy. B-cell acute myeloid leukemia (B-ALL) predominates in ALL, with current cure rates of ∼80%. However, the long-term survival rate of patients with early relapse or refractory B-ALL is very low. In recent years, Bromodomains and extra-terminal (BET) protein inhibitors have shown considerable prospect in hematological tumors. MZ1 is a novel BET inhibitor that degrades target proteins and inhibits tumor growth through proteolysis-targeting chimeras (PROTAC) technology. This study shows that MZ1 has cytotoxic effects on 697 (TCF3/PBX1) and RS4;11 (MLL-AF4) B-ALL cell lines representing different molecular subtypes of B-ALL. Furthermore, we observed that MZ1 could promote cell apoptosis, induce cells cycle arrest and inhibit B-ALL cell proliferation by depleting BET protein and downregulating the transcription of CCND3. Collectively, our results indicate that MZ1 might be exploited as a novel therapeutic strategy for the treatment of B-ALL. mRNA profiles of 697 cells treated with 1 μM MZ1 or same volume of DMSO for 24 h were generated by RNA sequencing, in double, using Illumina NovaSeq6000.