Prognostic Significance of TP53 Mutations and Single Nucleotide Polymorphisms in Acute Myeloid Leukemia: A case Series and Literature Review

Background: The response to treatment and overall survival (OS) of patients with acute myeloid leukemia(AML) is variable, with a median ranging from 6 months to 11.5 years. TP53 is associated with old age,chemotherapy resistance, and worse OS. Using genetic sequencing, we set out to look at our own experience withAML, and hypothesized that both TP53 mutations and SNPs at codon 72 would mimic the literature by occurringin a minority of patients, and conferring a worse OS. Materials and
Methods: We performed a pilot study ofrandomly selected, newly diagnosed AML patients at Mount Sinai Medical Center, diagnosed from 2005-2008(n=10). TP53 PCR sequencing was performed using DNA from bone marrow smears. Analysis was accomplishedusing Mutation Surveyor software with confirmation of the variants using the COSMIC and dbSNP databases.
Results: Fewer than half of the patients harbored TP53 mutations (40%). There was no significant differencein OS based on gender, AML history, risk-stratified karyotype, or TP53 mutation. There were possible trendstoward improved survival among patients less than 60 (11 vs 4 months, p=0.09), Hispanics (8 vs 1 months, p=0.11),and those not harboring SNP P72R (8 vs 2 months, p=0.10). There was a significant improvement in survivalamong patients with better performance status (28 vs 4 months, p=0.01) and those who did not have a complexkaryotype (8 vs 1 months, p=0.03). The most commonly observed TP53 mutation was a missense N310K (40%)and the most commonly observed SNP was P72R (100.0%).
Conclusions: Our study confirms previous reportsthat poor PS and the presence of a complex karyotype are associated with a decreased OS. In our cohort, TP53mutations were relatively common, occurring more frequently in male patients with an adverse karyotype.Although there was no significant difference in survival between TP53 mutated and un-mutated patients, therewas a possible trend toward worse OS among patients with SNP P72R. Larger studies are needed to validatethese findings.