Functional assessment of p53 in chronic lymphocytic leukemia

Several prognostic factors are used in chronic lymphocytic leukemia (CLL) to predict disease progression at diagnosis and to help guide therapeutic choices. Among these factors, the detection of deletions of the short arm of chromosome 17, where the tumor suppressor gene TP53 is located at the 17p13 locus, predicts resistance to standard treatments and poor prognosis.1 Deletions of 17p13 are observed in 5–7% of CLL patients at diagnosis and in 25–40% of cases with advanced refractory disease. Other markers of poor prognosis have been described, such as unmutated IGHV gene status, high levels of thymidine kinase and soluble CD23, CD38 and ZAP-70 expression, as well as other chromosomal aberrations, such as 11q23 deletion. However, defects in the TP53 pathway consistently appear as the most significant adverse prognostic factor in CLL.2