title: Wilms tumor gene single nucleotide polymorphism rs16754 predicts a favorable outcome in children with acute lymphoblastic leukemia.
abstract: OBJECTIVE
  Wilms tumor gene single nucleotide polymorphism (WT1 SNP) rs16754 has been described as a favorable risk marker in patients with acute myeloid leukemia. Subsequent studies revealed inconsistent results in both adult and pediatric patients. We analyzed its impact on clinical outcome in children with acute lymphoblastic leukemia (ALL) for the first time.
  
  
  METHODS
  WT1 SNP rs16754 of 158 children with ALL treated according to ALL Berlin-Frankfurt-Münster treatment trials from 1990 to 2009 and 43 hematopoietic stem cell donors was analyzed by allelic discrimination. WT1 SNP status was correlated with disease characteristics and clinical outcome comparing SNP (WT1(GG/AG)) and wildtype (WT1(AA)).
  
  
  RESULTS
  At least one minor allele was found in 23.4 % of patients and 34.9 % of donors (P = 0.07). Distribution of patient and disease characteristics was similar between WT1(GG/AG) and WT1(AA). In multivariate analyses, WT1 SNP was an independent good prognostic marker for cumulative incidence of relapse (CIR WT1(AA) vs. WT1(GG/AG) HR = 3.384, P = 0.021) and event-free survival (EFS; event risk WT1(AA) vs. WT1(GG/AG) HR = 2.503, P = 0.036). Univariate subanalyses of patients who underwent an allogeneic hematopoietic stem cell transplantation revealed more significant differences in CIR (P = 0.017), EFS (P = 0.012), and overall survival (OS; P = 0.017). Donor's WT1 SNP status did not affect outcome. We found no correlation between WT1 SNP and WT1 expression level at diagnosis (P = 0.634).
  
  
  CONCLUSIONS
  WT1 SNP rs16754 predicts improved CIR and EFS. Outcome differences were more prominent in transplanted children. Our findings identify WT1 SNP rs16754 as a favorable risk marker in pediatric ALL which is independent from known risk factors.
authors.affiliation: Department of Pediatrics, Jena University Hospital, Jena, Germany.
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Junghanns
authors.affiliation: Department of Pediatrics, Jena University Hospital, Jena, Germany.
authors.forename: Susan
authors.initials: S
authors.lastname: Wittig
authors.affiliation: Department of Pediatrics, Jena University Hospital, Jena, Germany.
authors.forename: Caroline
authors.initials: C
authors.lastname: Woehlecke
authors.affiliation: Institute of Medical Statistics, Computer Sciences and Documentation, Jena University Hospital, Jena, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Lehmann
authors.affiliation: Department of Pediatrics, Jena University Hospital, Jena, Germany.
authors.forename: Clemens
authors.initials: C
authors.lastname: Arndt
authors.affiliation: Department of Pediatrics, Jena University Hospital, Jena, Germany. bernd.gruhn@med.uni-jena.de.
authors.forename: Bernd
authors.initials: B
authors.lastname: Gruhn
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D015973:Gene Expression Regulation, Leukemic; D005838:Genotype; D018380:Hematopoietic Stem Cell Transplantation / Q000401:mortality*; D006801:Humans; D007223:Infant; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D011379:Prognosis; D015996:Survival Rate; D025721:WT1 Proteins / Q000235:genetics*; D055815:Young Adult
chemical_list: D025721:WT1 Proteins
keywords: Acute lymphoblastic leukemia (ALL); Pediatrics; Single nucleotide polymorphism (SNP); Wilms tumor gene 1 (WT1); rs16754