WT1 mutations in T-ALL

Blood. 2009 Jul 30;114(5):1038-45. doi: 10.1182/blood-2008-12-192039. Epub 2009 Jun 3.


The molecular mechanisms involved in disease progression and relapse in T-cell acute lymphoblastic leukemia (T-ALL) are poorly understood. We used single nucleotide polymorphism array analysis to analyze paired diagnostic and relapsed T-ALL samples to identify recurrent genetic alterations in T-ALL. This analysis showed that diagnosis and relapsed cases have common genetic alterations, but also that relapsed samples frequently lose chromosomal markers present at diagnosis, suggesting that relapsed T-ALL emerges from an ancestral clone different from the major leukemic population at diagnosis. In addition, we identified deletions and associated mutations in the WT1 tumor suppressor gene in 2 of 9 samples. Subsequent analysis showed WT1 mutations in 28 of 211 (13.2%) of pediatric and 10 of 85 (11.7%) of adult T-ALL cases. WT1 mutations present in T-ALL are predominantly heterozygous frameshift mutations resulting in truncation of the C-terminal zinc finger domains of this transcription factor. WT1 mutations are most prominently found in T-ALL cases with aberrant rearrangements of the oncogenic TLX1, TLX3, and HOXA transcription factor oncogenes. Survival analysis demonstrated that WT1 mutations do not confer adverse prognosis in pediatric and adult T-ALL. Overall, these results identify the presence of WT1 mutations as a recurrent genetic alteration in T-ALL.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Child
  • Chromosome Aberrations
  • Clone Cells / chemistry
  • DNA Methylation
  • DNA Mutational Analysis
  • DNA, Neoplasm / genetics
  • Disease Progression
  • Genes, Homeobox
  • Genes, Wilms Tumor*
  • Humans
  • Kaplan-Meier Estimate
  • Mutation*
  • Neoplasm Proteins / chemistry
  • Neoplasm Proteins / genetics
  • Oncogenes
  • Polymorphism, Single Nucleotide
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / mortality
  • Prognosis
  • Recurrence
  • WT1 Proteins / chemistry
  • WT1 Proteins / genetics
  • Zinc Fingers / genetics


  • DNA, Neoplasm
  • Neoplasm Proteins
  • WT1 Proteins

Associated data

  • GEO/GSE15931