Cytoplasmic sequestration of wild-type p53 in a patient with therapy-related resistant AML: first report.

p53 inactivation is a key factor in human tumorigenesis and chemotherapy resistance. The traditionally described mechanisms of p53 inactivation in acute myeloid leukemia (AML) include TP53 mutations and abrogation of p53 pathway. Malfunction of wild-type (wt) p53, due to its cytoplasmic mislocalization, has been described, thus far, only in solid tumors.

Identification of gene networks associated with erythroid differentiation.

Erythropoiesis is a multistep process involving a large number of genes, which balance between proliferation, differentiation and survival of the erythroid cells. To understand the molecular mechanisms of erythropoiesis and related pathological aberrations, we analyzed three stages of in vitro differentiating human erythroid cells by expression profiling. We identified distinct clusters of genes, each with a unique expression pattern during differentiation.

The onset of p53-dependent apoptosis plays a role in terminal differentiation of human normoblasts.

The p53 tumor suppressor gene was found to play a role in the differentiation of several tissue types. We report here that p53-dependent apoptosis plays a role in the final stages of physiological differentiation of normoblasts, resulting in nuclear condensation and expulsion without cell death. Blood samples of healthy newborns, cord blood as well as bone marrow, were analysed for apoptosis by TUNEL and p53 expression by immunostaining.

TP53 in hematological cancer: low incidence of mutations with significant clinical relevance.

Inactivation of the wild-type p53 gene (TP53) by various genetic alterations is a major event in human tumorigenesis. More than 60% of human primary tumors exhibit a mutation in the p53 gene. Hematological malignancies present a rather low incidence of genetic alterations in this gene (10-20%).