p53 and hematological malignancies

Abstract

p53 is a tumor-suppressor gene encoding a nuclear phosphoprotein that plays an important role in the control of normal cell proliferation, repair of DNA damage and apoptosis. Upon cellular stress, particularly the one induced by DNA danage, p53 protein can arrest cell cycle progression, thus allowing the DNA to be repaired; or it can lead to apoptosis. These functions are achieved by the transcriptional properties of p53, which activates a group of genes involved in cell cycle regulation. Mutant p53 is no longer able to control cell proliferation, resulting in inefficient DNA repair and emergence the genetically unstable cells. The most common changes of p53 cancers are point mutations within the coding sequences of this gene. In hematological malignancies, mutations of p53 gene or inactivation and stabilization of p53 protein are less common than in solid tumor, and usually consist in missense mutations. In hematological malignancies, these alterations are more observed in the evolution from the chronic phase to blast crisis of chronic mieloid leukemia, from myelodysplastic to acute myeloid leukemia, from follicular to high-grade lymphoma, from chronic lymphoid leukemia to high-grade Richter´s syndrome, and from relapsed of acute leukemias. The objective of this review is to characterize the p53 abnormalities in hematological malignancies and discuss the clinical significance of these genetic alterations in the pathogenesis and prognosis.