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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.

Publication ,  Journal Article
Becker, H; Maharry, K; Radmacher, MD; Mrózek, K; Metzeler, KH; Whitman, SP; Schwind, S; Kohlschmidt, J; Wu, Y-Z; Powell, BL; Carter, TH ...
Published in: Haematologica
October 2011

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.

Duke Scholars

Published In

Haematologica

DOI

EISSN

1592-8721

Publication Date

October 2011

Volume

96

Issue

10

Start / End Page

1488 / 1495

Location

Italy

Related Subject Headings

  • Young Adult
  • WT1 Proteins
  • Prognosis
  • Polymorphism, Single Nucleotide
  • Nucleophosmin
  • Middle Aged
  • MicroRNAs
  • Male
  • Leukemia, Myeloid, Acute
  • Immunology
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Becker, H., Maharry, K., Radmacher, M. D., Mrózek, K., Metzeler, K. H., Whitman, S. P., … Bloomfield, C. D. (2011). 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. Haematologica, 96(10), 1488–1495. https://doi.org/10.3324/haematol.2011.041905
Becker, Heiko, Kati Maharry, Michael D. Radmacher, Krzysztof Mrózek, Klaus H. Metzeler, Susan P. Whitman, Sebastian Schwind, et al. “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.Haematologica 96, no. 10 (October 2011): 1488–95. https://doi.org/10.3324/haematol.2011.041905.
Becker H, Maharry K, Radmacher MD, Mrózek K, Metzeler KH, Whitman SP, Schwind S, Kohlschmidt J, Wu Y-Z, Powell BL, Carter TH, Kolitz JE, Wetzler M, Carroll AJ, Baer MR, Moore JO, Caligiuri MA, Larson RA, Marcucci G, Bloomfield CD. 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. Haematologica. 2011 Oct;96(10):1488–1495.

Published In

Haematologica

DOI

EISSN

1592-8721

Publication Date

October 2011

Volume

96

Issue

10

Start / End Page

1488 / 1495

Location

Italy

Related Subject Headings

  • Young Adult
  • WT1 Proteins
  • Prognosis
  • Polymorphism, Single Nucleotide
  • Nucleophosmin
  • Middle Aged
  • MicroRNAs
  • Male
  • Leukemia, Myeloid, Acute
  • Immunology