Proteomics of p53 in Diagnostics and Therapy of Acute Myeloid Leukemia

Nina      Anensen; Ingvild      Haaland; Clive      D'Santos; Werner Van Belle; Bjorn Tore Gjertsen

doi:10.2174/138920106777549731

Abstract

The anti-oncogene TP53 is frequently mutated in human cancer, but in hematological malignancies this is arare feature. In acute myeloid leukemia (AML) more than 90% of the patients comprise wild type TP53 in their cancercells, but if TP53 is mutated or deleted the disease is often found to be chemoresistant. In this review we define pro-teomics of the oncogene product p53 as the study of proteins in the p53 regulating signaling networks, as well as the pro-tein study of members of the p53 family itself. Various messenger RNA splice forms as well as a multitude of post-translational modifications give a high number of protein isoforms in the p53 family. Some of the proteomic techniquesallow detection of various isoforms, such as two-dimensional gel electrophoresis in combination with tandem mass spec-trometry (MS/MS) and this methodology may therefore increasingly be used as a diagnostic tool in human disease. Weintroduce the p53 protein as an illustration of the complexity of post-translational m odifications that may affect one highlyconnected protein and discuss the possible impact in AML diagnostics if the p53 profile is reflecting cell stress and statusof signal transduction systems of the malignancy.

Keywords: p53, AML, diagnosis, therapy, signaling networks, two-dimensional electrophoresis

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