Abstract
The TP53 mutation is frequently detected in acute myeloid leukemia (AML) patients with complex karyotype (CK), but the stability of this mutation during the clinical course remains unclear. In this study, TP53 mutations were identified in 7% of 500 patients with de novo AML and 58.8% of patients with CK. TP53 mutations were closely associated with older age, lower white blood cell (WBC) and platelet counts, FAB M6 subtype, unfavorable-risk cytogenetics and CK, but negatively associated with NPM1 mutation, FLT3/ITD and DNMT3A mutation. Multivariate analysis demonstrated that TP53 mutation was an independent poor prognostic factor for overall survival and disease-free survival among the total cohort and the subgroup of patients with CK. A scoring system incorporating TP53 mutation and nine other prognostic factors, including age, WBC counts, cytogenetics and gene mutations, into survival analysis proved to be very useful to stratify AML patients. Sequential study of 420 samples showed that TP53 mutations were stable during AML evolution, whereas the mutation was acquired only in 1 of the 126 TP53 wild-type patients when therapy-related AML originated from different clone emerged. In conclusion, TP53 mutations are associated with distinct clinic-biological features and poor prognosis in de novo AML patients and are rather stable during disease progression.
Highlights
TP53 mutations in patients with de novo acute myeloid leukemia (AML) A total of 36 different TP53 mutations were identified in 35 patients (Table 1 and Figure 1)
We found that the TP53 mutation was associated with distinct clinic-biological features and was a poor prognostic factor in AML patients, independent of age, white blood cell (WBC) counts, karyotype and other genetic markers
Most TP53 mutations were found in exons 5–8,30,31 and few mutations occurred outside exons 5–8.9 We analyzed exons 3–9 in this study to avoid missing some mutations outside exons 5–8
Summary
Several studies have shown TP53 mutations are frequently detected in patients with therapy-related acute myeloid leukemia (AML)[7] or AML with complex karyotype (AML-CK).[8,9,10] The incidences of this mutation in AML-CK varied from 53% in a British series,[10] to 60–69% in two German studies.[8,9] In contrast, TP53 mutations rarely occurred in patients without CK (2.1%)[8] or 17p chromosomal abnormality (2.8%).[11] The reports regarding the prognostic relevance of TP53 mutations in patients with AML-CK showed controversial results. Rucker et al.[9] showed that TP53 mutation was an independent poor risk factor for overall survival (OS) in AML patients with CK; the same finding could not be shown by Bowen et al.[10]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
