A clinical guide to TP53 mutations in myeloid neoplasms

ABSTRACT: TP53 mutations are found in 10% to 15% of myeloid neoplasms and are one of its most important prognostic factors. Emerging data show that TP53 mutational allele status is a key determinant of clinical outcomes, with multihit TP53 mutant myeloid neoplasms having a very poor prognosis. Significant differences exist among the methods used in clinical and research settings to assess TP53 mutational status, leading to variability in reported patient characteristics, response to therapy, and survival. Indeed, differences in the criteria used to define TP53 mutational states among professional societies and in landmark research studies have led to confusion, suboptimal clinical testing, and variability in therapy recommendations. We review the methods used to assess for TP53 mutational allele status and provide recommendations, based on clinically available testing, for the accurate evaluation of TP53 gene mutations in myeloid neoplasms. Hotspot mutations represent ∼35% of all TP53 missense mutations in myeloid neoplasms. There is evidence that these hotspot mutations may have dominant-negative or gain-of-function properties. Here, we review this evidence and discuss the potential impact of TP53 mutation identity on patient outcomes and clinical management.