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

Abstract

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%). Nevertheless, epidemiological studies of the hematological malignancies indicate that the prognosis of patients with a mutation in the p53 gene is worse than those expressing the wild‐type p53 protein. Correlations between drug resistance, altered apoptosis, and mutations in the p53 gene are found in hematological malignancies and leukemias. These issues, as well as the possibility of exploiting p53 and its various functions for new therapeutic strategies, are discussed in the present review. Hum Mutat 21:277–284, 2003. © 2003 Wiley‐Liss, Inc.

p53 flow cytometry evaluation in leukemias: Correlation to factors affecting clinical outcome

“…Correlations between aberrations of chromosome 17 and mutations of p53 gene have been found during this process and several studies have reported structural alterations of chromosome 17, mutations of p53 gene and p53 protein expression in BP (6)(7)(8)33,34). The reported frequency of p53 alterations in BP of CML is about 30% (33).…”

“…p53 mutations are present in less than 5% of children with ALL at initial presentation (7). Mutations were detected more frequently in children with relapsed T-cell ALL.…”

“…The presence of p53 protein expression has been associated with worse prognosis for several types of tumors including hematological neoplastic diseases (5)(6)(7)(8). In this study, FC method was selected due to its easiness of accomplishment and interpretation, which is attractive considering that the main focus on this work is the translation of the results to the clinical setting.…”

“…Although the alterations are rare in malignant hematological disorders, these genetic alterations have a strong correlation with unfavorable clinical factors, and it have been observed in patients with relapse of acute lymphoid leukemia (ALL), secondary acute myeloid leukemia (AML), acute phase of chronic myeloid leukemia (CML), and evolution from chronic lymphoid leukemia (CLL) to Richter's syndrome (CLL/ SR) (5)(6)(7)(8). Therefore, p53 protein expression analysis may be a valuable way of assessing the functional status of p53 gene in hematological malignancies.…”

Mutant p53 gain of function can be at the root of dedifferentiation of human osteosarcoma MG63 cells into 3AB-OS cancer stem cells

“…TP53 mutations occur in almost every type of cancer at rates varying between 10% in hematopoietic malignancies [38] and 98% in high-grade serous carcinoma of the ovary [39]. Unlike the majority of tumor suppressor genes, which are inactivated by deletions or truncated mutations, TP53 mostly undergoes missense mutations [40].…”