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Blood, Vol. 112, Issue 3, 793-804, August 1, 2008
Vorinostat synergistically potentiates MK-0457 lethality in chronic myelogenous leukemia cells sensitive and resistant to imatinib mesylate
Blood Dai et al.
112: 793
Supplemental materials for: Dai et al
Files in this Data Supplement:
- Figure S1. Vorinostat enhances the lethality of MK-0457 in primary CML cells (JPG, 44.1 KB)
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Primary CML cells (patients #1 and #3) were exposed to 100nM – 500nM MK0457 in the absence or presence of 1.5µM or 2µM vorinostat for 48hr, after which the percentage of 7AAD+ cells was determined by flow cytometry. The results represent the means ± SD for experiments performed in triplicate.
- Figure S2. Interactions between vorinostat and MK-0457 in parental Ba/F3 cells and in Ba/F3 cells expressing wt or T315I Bcr/Abl (JPG, 120 KB)
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(A) Parental Ba/F3 cells and Ba/F3 cells transfected with wt Bcr/Abl or a T315I Bcr/Abl mutant were exposed to 300nM MK-0457 ± 1.5µM vorinostat for 48h. (B) Parental Ba/F3 cells were exposed to 100nM MK-0457 ± 1µM vorinostat for 48h. After treatment, cells were stained with both DiOC6 and 7AAD and subjected to flow cytometry. “Low” DiOC6 uptake/7AAD− (lower left quadrant) corresponds to early apoptosis (mitochondrial damage, reflected by loss of Δψm) and “low” DiOC6/7AAD+ (upper left quadrant) to late apoptosis. Values reflect the percentage of cells in the corresponding quadrants. The results of a representative experiment are shown; an additional experiment yielded equivalent results. Veh = vehicle.
- Figure S3. Vorinostat diminishes the association between Hsp90 and Bcr/Abl, in LAMA84 cells exposed to MK-0457 (JPG, 49 KB)
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LAMA84 cells were exposed to 100nM MK-0457 ± 1.5µM vorinostat for 16h, after which co-immunoprecipitation (IP) was performed using a c-Abl antibody followed by Western blot analysis using an Hsp90 antibody as described in “Materials and Methods” (upper panels). Alternatively, Western blot analysis was performed to monitor levels of Bcr/Abl protein (bottom panel). Veh = vehicle. An additional 2 studies yielded equivalent results.
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