Clinical outcome and gene- and microRNA-expression profiling according to the wilms tumor 1 (WT1) single nucleotide polymorphism rs16754 in adult de novo cytogenetically normal acute myeloid leukemia: A cancer and leukemia group B study

Academic Article

Abstract

  • Background The alleles of the Wilms tumor 1 (WT1) polymorphism rs16754 harbor adenine (A) or guanine (G). Recently, rs16754 has been reported to affect the outcome of patients with cytogenetically normal acute myeloid leukemia. To validate this finding, we investigated pretreatment features and outcome associated with rs16754 in a large cohort of patients with cytogenetically normal acute myeloid leukemia. Design and Methods Four-hundred and thirty-three intensively treated and molecularly characterized cytogenetically normal patients with de novo acute myeloid leukemia (18-83 years old) were analyzed for rs16754. To gain biological insights, we studied the gene- and microRNA-expression profiles for associations with rs16754. Results Three-hundred and nine (71%) patients were homozygous for A (WT1 AA), 112 (26%) were heterozygous (WT1 AG) and 12 (3%) were homozygous for G (WT1 GG). For comparison with previous studies, we grouped WT1 AG and WT1 GG patients and compared them with WT1 AA patients divided into younger (<60 years) and older (≥60 years) adults. We found no independent prognostic impact of WT1 AA. However, WT1 GG patients, who were less often Caucasian than WT1 AG (P=0.001) or WT1 AA (P=0.008) patients, and had TET2 mutations more often than WT1 AG (P=0.02) patients, had, among patients with FLT3-internal tandem duplication and/or NPM1 wild-type, better disease-free (P=0.02) and overall survival (P=0.04) than WT1 AA and WT1 AG patients combined. Unsupervised and supervised analyses of the gene- and microRNA-expression profiles suggested that there were no distinct expression patterns associated with any rs16754 genotype. Conclusions We did not observe the previously reported adverse impact of WT1 AA but found favorable outcomes associated with the homozygous WT1 GG. Considering its low frequency, confirmatory studies are necessary. The biological significance of rs16754 remains questionable as no distinct expression profiles were associated with the genotypes. © 2011 Ferrata Storti Foundation.
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    Author List

  • Becker H; Maharry K; Radmacher MD; Mrózek K; Metzeler KH; Whitman SP; Schwind S; Kohlschmidt J; Wu YZ; Powell BL
  • Start Page

  • 1488
  • End Page

  • 1495
  • Volume

  • 96
  • Issue

  • 10