[Clinical and prognostic values of TP53 mutation in patients with acute myeloid leukemia]

Objective: To explore the clinical and prognostic values of TP53 gene mutation in patients with acute myeloid leukemia (AML) . Methods: A retrospective analysis of 265 newly diagnosed AML patients with next-generation sequencing (NGS) data in the Hematology Department of Changhai Hospital from January 2010 to January 2019 was performed. Mutation analysis was carried out by targeted sequencing technology including 200 hematological malignancy related genes. The association of TP53 mutation with clinical features was analyzed. Results: Alterations in TP53 were found in 20 (7.5%) patients, including 17 case (6.4%) of missense mutations, 2 cases (0.7%) of frame-shift deletion mutations and 1 case (0.4%) of splicing sites mutation. A total of 23 kinds of TP53 mutations were detected, most of them (16, 69.6%) were located in the DNA binding domain of exon 5-8, 4 in the DNA binding domain of exon 3-4, 2 in exon 10 and 1 in splice site, respectively. The median age of patients with TP53 alterations was higher than those without [52 (26-72) years old vs 45 (14-75) years old, P= 0.008]. The frequency of complex karyotypes was higher in patients with TP53 alterations than those without [45.0% (9/20) vs 6.1% (15/245) , P<0.001]. Median overall survival (OS) of patients with TP53 alterations was shorter than those without[14.1 (95%CI 6.78-21.42) months vs 31.4 (95%CI 13.20-49.59) months, P=0.029]. The OS of patients treated with "Decitabine + CAG" was superior than that of patients treated with "3 + 7" regimen [30.0 (95%CI 27.35-38.84) months vs 12.5 (95%CI 5.80-19.19) months, P=0.018]. Multivariate analysis indicated that TP53, DNMT3A and USH2A alterations, WBC ≥ 12.45×10(9)/L had negative impacts on OS. Conclusion: The frequency of TP53 mutation was 7.5% in our cohort. Most mutations were located in the DNA binding domain. TP53 alterations were strongly associated with older age, complex karyotype and shorter OS. Decitabine-based induction chemotherapy and hematopoietic stem cell transplantation may improve OS, more cases and/or multicenter randomized studies are needed for further confirmation.