[Show abstract][Hide abstract] ABSTRACT: Aberrations of TP53 (mutations and/or deletions) are associated with a dismal prognosis in chronic lymphocytic leukemia (CLL). Complete loss of ATM is another mechanism of failed DNA damage response and also associated with poorer prognosis in CLL. However, p53 dysfunction may arise through alternative mechanisms unrelated to structural aberrations (deletion and/or mutation) of TP53 or ATM, and thus be undetectable by traditional DNA-directed approaches (fluorescence in situ hybridization [FISH], sequencing, karyotyping). In order to address the latter changes, and also to better understand the consequences of TP53/ATM aberrations, p53 functional assays have recently been developed. The purpose of dynamic assessment of p53 response in CLL is to carry out a comprehensive analysis of all mechanisms causing p53-deficient phenotype, including those unrelated to genomic aberrations of TP53 and ATM. The present review focuses on the current knowledge of p53 function assays in CLL, including important features such as technical issues, correlation with structural aberrations and clinical value.
[Show abstract][Hide abstract] ABSTRACT: Twist1 and Twist2 (Twist1-2) are two transcription factors, members of the basic helix-loop-helix family, that have been well established as master transcriptional regulators of embryogenesis and developmental programs of mesenchymal cell lineages. Their role in oncogenesis in epithelium-derived cancer and in epithelial-to-mesenchymal transition has also been thoroughly characterized. Recently, emerging evidence also suggests a key role for Twist1-2 in the function and development of hematopoietic cells, as well as in survival and development of numerous hematological malignancies. In this review, we summarize the latest data that depict the role of Twist1-2 in monocytes, T cells and B lymphocyte activation, and in associated hematological malignancies.
Blood Cancer Journal 01/2014; 4:e206. · 1.40 Impact Factor
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