Introduction: We investigated the effect of two antisense oligodeoxynucleotides, previously selected with the help of computer-aided RNA structure prediction, on drug sensitivity, bcl-2 expression and apoptosis of leukemia cells. The drugs tested were etoposide (VP-16), cytarabine (Ara-C), daunorubicin (DNR) and arsenic trioxide (As2O3). Materials and methods: The experimental assays were performed with cultures, IC50 of leukemic cells to drugs, immunochemistry and flow cytometry. Results: The results showed that the two antisense oligodeoxynucleotides significantly reduced IC50 levels for VP-16, Ara-c, DNA and As2O3, inhibited bcl-2 gene expression and induced apoptosis of leukemic cells. Conclusions: Computational prediction of antisense efficacy is faster than other methods and more cost-efficient. This could hasten the development of sequences for both research and clinical applications.