Gene expression profile of K562 and KBM5 treated with the combination of imatinib and a new demethylating agent, OR-2100

Treatment with demethylating agents in combination with tyrosine kinase inhibitors have shown improved molecular responses and survival benefits in patients with TKI-resistant or advanced-phase CML. However, little is known regarding underlying mechanism of the combination anti-tumor effect of demethylating agents and tyrosine kinase inhibitors. To analyze the combination effect, we have compared gene expression profiles among chronic myeloid leukemia (CML) cell lines (K562, KBM5) treated with imatinib (IM), a new demethylating agent, OR-2100 (OR21), and these combination therapy. To identify specific gene expressions of the combination therapy of imatinib and OR21 against CML cells, gene array analysis was performed. K562 and KBM5 cells were pre-exposed with OR21 for 3 consecutive days, then followed by IM exposure. Total RNA of each treated cells in each cell line was extracted 24 hours after IM exposure and gene expressions were compared among 4 groups; control (no exposure), OR21, IM, and the combination.