Inactivation of the tumor suppressor function of the p53 gene is found in association with 20-40% cases of chronic myeloid leukemia (CML) in blast crisis. A common mechanism of p53 inactivation in CML is by complete deletion of one p53 allele in association with a point mutation which produces a mutant p53 protein on the remaining allele. Whether the mutant p53 protein, which is generally expressed at an elevated level, plays any role in the pathogenesis of blastic transformation or in maintaining the neoplastic proliferation, as it does in some solid tumors, is unknown. By using an antisense oligonucleotide approach, we investigated the cellular function of known abnormal forms of p53 protein, both mutant and truncated, expressed in CML cell lines. We found that the introduction of p53 antisense oligonucleotides can specifically inhibit the translation of the p53 mRNA. However, inhibiting p53 expression had no effect on cell proliferation, cell viability, and colony formation. There was no change in cell doubling time when the cells were maintained in serum-free medium (SFM) in the presence of antisense oligonucleotides compared with cells maintained in SFM alone. We conclude that the mutant or truncated p53 proteins expressed in the blast cells of CML have no growth-promoting effect and are not required for cell survival and proliferation. We further speculate that the loss of the tumor suppressor function of p53 might be the only mechanism by which p53 is involved in the transition from chronic phase to blast crisis.