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WT1 mutations are secondary events in AML, show varying frequencies and impact on prognosis between genetic subgroups

M-T Krauth1, T Alpermann2, U Bacher2

  • 11] MLL Munich Leukemia Laboratory, Munich, Germany [2] Division of Hematology and Hemostaseology, Department of Internal Medicine I, Medical University Vienna, Vienna, Austria.

Leukemia
|August 12, 2014
PubMed

Insights

Wilms tumor 1 (WT1) mutations are found in 5.5% of acute myeloid leukemia patients and are more common in females and younger individuals. WT1 mutations independently predict a worse event-free survival in normal karyotype AML.

Area of Science:

  • Hematology
  • Molecular Oncology
  • Genetics

Background:

  • Wilms tumor 1 (WT1) gene mutations are implicated in various cancers.
  • Understanding the frequency and prognostic significance of WT1 mutations in acute myeloid leukemia (AML) is crucial for patient stratification and treatment strategies.

Purpose of the Study:

  • To determine the frequency of WT1 mutations (mut) in a large cohort of unselected acute myeloid leukemia (AML) patients.
  • To investigate the prognostic impact of WT1 mutations on patient survival outcomes.

Main Methods:

  • Analysis of WT1 mutations in exons 7 and 9 from 3157 unselected AML patients.
  • Correlation of WT1 mutation status with clinical characteristics, cytogenetics, and molecular mutations (CEBPA, PML-RARA, FLT3-ITD, DNMT3A, ASXL1, IDH1/2).
  • Evaluation of WT1 mutation stability in paired samples and assessment of prognostic impact using event-free survival (EFS) in univariate and multivariate analyses.

Main Results:

  • WT1 mutations were detected in 5.5% (175/3157) of AML patients, with higher frequencies observed in those with biallelic CEBPA mutations, t(15;17)/PML-RARA, and FLT3-ITD.
  • WT1 mutations were more frequent in females and patients younger than 60 years.
  • In normal karyotype AML, WT1 mutations were associated with shorter event-free survival (EFS). Multivariate analysis confirmed WT1 mutations as an independent adverse prognostic factor for EFS, alongside FLT3-ITD and age.

Conclusions:

  • WT1 mutations occur in a subset of AML patients and their frequency varies across different genetic subgroups.
  • WT1 mutations demonstrate relative instability between diagnosis and relapse.
  • WT1 mutations serve as an independent adverse prognostic marker for event-free survival in AML, particularly in patients with a normal karyotype.

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