OBJECTIVE: The protooncogene c-Myc plays an important role in the control of 
cell proliferation, apoptosis, and differentiation, and its aberrant expression 
is frequently seen in multiple human cancers, including acute myeloid leukemia 
(AML). As c-Myc heterodimerizes with Max to transactivate downstream target 
genes in leukemogenesis. Inhibition of the c-Myc/Max heterodimerization by the 
recently identified small-molecule compound, 10058-F4, might be a novel 
antileukemic strategy.
MATERIALS AND METHODS: HL-60, U937, and NB4 cells and primary AML cells were 
used to examine the effects of 10058-F4 on apoptosis and myeloid 
differentiation.
RESULTS: We showed that 10058-F4 arrested AML cells at G0/G1 phase, 
downregulated c-Myc expression and upregulated CDK inhibitors, p21 and p27. 
Meanwhile, 10058-F4 induced apoptosis through activation of mitochondrial 
pathway shown by downregulation of Bcl-2, upregulation of Bax, release of 
cytoplasmic cytochrome C, and cleavage of caspase 3, 7, and 9. Furthermore, 
10058-F4 also induced myeloid differentiation, possibly through activation of 
multiple transcription factors. Similarly, 10058-F4-induced apoptosis and 
differentiation could also be observed in primary AML cells.
CONCLUSION: Our study has shown that inhibition of c-Myc/Max dimerization with 
small-molecule inhibitors affects multiple cellular activities in AML cells and 
represents a potential antileukemic approach.