title: Prognostic significance of TP53 mutations and single nucleotide polymorphisms in acute myeloid leukemia: a case series and literature review.
abstract: 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 with AML, and hypothesized that both TP53 mutations and SNPs at codon 72 would mimic the literature by occurring in a minority of patients, and conferring a worse OS.
  
  
  METHODS
  We performed a pilot study of randomly 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 accomplished using 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 difference in OS based on gender, AML history, risk-stratified karyotype, or TP53 mutation. There were possible trends toward 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 survival among patients with better performance status (28 vs 4 months, p=0.01) and those who did not have a complex karyotype (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 reports that poor PS and the presence of a complex karyotype are associated with a decreased OS. In our cohort, TP53 mutations 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, there was a possible trend toward worse OS among patients with SNP P72R. Larger studies are needed to validate these findings.
authors.affiliation: Department of Internal Medicine, Mount Sinai Medical Center, Miami Beach, Florida, USA E-mail : simonzeichner@gmail.com.
authors.forename: Simon Blechman
authors.initials: SB
authors.lastname: Zeichner
authors.forename: Sarah
authors.initials: S
authors.lastname: Alghamdi
authors.forename: Gina
authors.initials: G
authors.lastname: Elhammady
authors.forename: Robert John
authors.initials: RJ
authors.lastname: Poppiti
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use; D001483:Base Sequence; D003630:Daunorubicin / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D000903:Antibiotics, Antineoplastic; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D003630:Daunorubicin