cells were treated with increasing concentrations from each drug alone and in combination, maintaining the same concentration ratio of bortezomib/paclitaxel. Dose-effect curves for single treatments with bortezomib and paclitaxel were previously determined in K562, LAMA84 or Baf3 Bcr-Abl cells by us or other groups. To assess bortezomib/paclitaxel interaction in Bcr-Abl positive cells, K562 and LAMA84 were exposed to 9nM or 4nM bortezomib, alone or in combination with paclitaxel, for 48h. Specifically, 9nM bortezomib in combination with 6nM paclitaxel induces cell death in K562, while each treatment alone induces less than 21% cell death, as measured with Trypan Blue exclusion assay. The Naringoside Combined treatment results in a decrease in procaspase 3, as well as a significant increase in cleavage of the initiator caspases 8 and 9 and the effector caspase 3, in K562 cells. This indicates activation of caspases, and suggests the involvement of both the extrinsic and intrinsic pathways of apoptosis. In order to analyze the direct activity of caspases on their known substrates, we have detected the Poly Polymerase cleavage by Western blot. PARP is a well established substrate for many caspases. PARP cleavage was significantly enhanced in the combined treatment compared with each treatment alone underscoring caspase activation during bortezomib/paclitaxelinduced cell death. Similarly, LAMA84 cell treated with 4nM bortezomib in combination with paclitaxel resulted in 41% cell death, while single treatments induce cell death. Combined treatment induced a decrease of pro-caspase 3 and a significant increase in cleaved fragments of caspases 3, 8, 9. These results correlate with an increase in PARP cleavage We further confirmed these results by analyzing bortezomib/ paclitaxel-induced cell death/apoptosis with Annexin V/7AAD and the effect on viability/proliferation with MTT assay, in K562. Moreover, the effect on proliferation was also determined. Notably, while in the control and bortezomib treatments, 90min of BrdU MRT68921 (hydrochloride) distributor exposure resulted in a BrdU incorporation of 65.1% and 60.1% cells respectively, in paclitaxel treated cells and combination the proliferation is significantly decreased. Combined treatment has less effect on proliferation compared to paclitaxel alone, suggest