TP53 in adult acute lymphoblastic leukemia

Abstract

Acute lymphoblastic leukemia (ALL) is characterized by a great biological and clinical heterogeneity. Despite most adult patients enter complete hematologic remission after induction therapy only 40% survive five or more years. Over the last 20 years, the definition of an accurate biologic leukemia profile and the minimal residual disease evaluation in addition to conventional risk criteria led to a significant improvement for the risk stratification. The alterations of the oncosuppressor gene TP53, including deletions, sequence mutations and defect in its expression due to regulatory defects, define a new important predictor of adverse outcome. More recently, new drugs have been developed with the aim of targeting p53 protein itself or its regulatory molecules, such as Mdm2, and restoring the pathway functionality. Therefore, TP53 alterations should be considered in the diagnostic work-up to identify high risk ALL patients in need of intensive treatment strategies or eligible for new innovative targeted therapies.

Keywords: TP53; acute lymphoblastic leukemia; next generation sequencing; prognostic factors.