Several recent studies indicate that the p53 tumor suppressor pathway is often inactivated in de novo myeloid leukemia through oncogenic-specific mechanisms, which converge on aberrant p53 protein deacetylation.
Thus, overexpression of sPRDM16 induces abnormal growth of stem cells and progenitors and cooperates with disruption of the p53 pathway in the induction of myeloid leukemia.
The activations of the ras oncogenes or inactivation of the p53 anti-oncogene by point mutations have been described recently in several cases of MDS as well as AML, suggesting a critical role for these alterations in the development of these myelogenous leukemias.
Since p53 has been implicated in lymphatic and some myeloid leukemias, such as the blastic phase of chronic myelogenous leukemia, we sought to address the role of p53 gene mutations within exons 4-9 in myelodysplastic syndromes (MDS), a myeloid preleukemic condition.