Oligodeoxynucleotide-based therapeutics for human leukemias

As the cell and molecular biology of hematopoietic cell development becomes known in greater detail, the roles of individual genes in regulating cell proliferation and growth also become better appreciated. Some genes appear to be of particular importance in these complex processes and are therefore potential targets for molecularly based therapeutics. The rationale for such treatment is that, if the function of critical genes can be efficiently and specifically perturbed, then the ensuing disruption might lead to preferential leukemic cell death. Several technologies for carrying out targeted gene disruption now exist. One approach, the "antisense" gene strategy, appears to be particularly well suited to the treatment of human leukemia ex vivo and perhaps in vivo as well. Herein I review the experience of my laboratory in using this approach to target the c-myb and c-kit proto-oncogenes in human leukemic cells. Our results suggest that use of oligodeoxynucleotides for disrupting the function of specific genes may prove useful for both ex vivo and in vivo treatment of patients with hematopoietic malignancies.