The development of resistance to imatinib mesylate may partly depend on high 
bcr-abl expression levels or point mutation(s). Arsenic trioxide (ATO) has 
bcr-abl suppressing activity in vitro, without cross-resistance to imatinib. 
Meanwhile, bcr-abl also induces expression of vascular endothelial growth factor 
(VEGF), which is associated with tumor-related angiogenesis and is involved in 
chronic myelogenous leukemia (CML) pathogenesis. Here, we investigated ways to 
improve ATO activity in CML by modulating cellular VEGF levels. K562 and primary 
CML cells were transfected with a VEGF antisense sequence. Cell viability and 
survival were assessed using 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium 
bromide and trypan blue exclusion assays. Apoptotic cells were detected by flow 
cytometry following annexin V and propidium iodide staining. The results showed 
that VEGF depletion effectively promotes enhanced ATO antileukemic activity by 
repressing bcr-abl protein levels. These data provide a rationale for the 
clinical development of optimized ATO-based regimens that incorporate VEGF 
modulator for CML treatment.