WT1 mutations in T-ALL

Valeria Tosello, Marc R. Mansour, Kelly Barnes, Maddalena Paganin, Maria Luisa Sulis, Sarah Jenkinson, Christopher G. Allen, Rosemary E. Gale, David C. Linch, Teresa Palomero, Pedro Real, Vundavalli Murty, Xiaopan Yao, Susan M. Richards, Anthony Goldstone, Jacob Rowe, Giuseppe Basso, Peter H. Wiernik, Elisabeth M. Paietta, Rob PietersMartin Horstmann, Jules P P Meijerink, Adolfo A. Ferrando

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)1038-1045
Number of pages8
JournalBlood
Volume114
Issue number5
DOIs
StatePublished - 2009

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Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
T-cells
Mutation
Pediatrics
Transcription Factors
Frameshift Mutation
Sequence Deletion
Zinc Fingers
Survival Analysis
Tumor Suppressor Genes
Polymorphism
Oncogenes
Single Nucleotide Polymorphism
Disease Progression
Zinc
Tumors
Nucleotides
Clone Cells
Genes
Recurrence

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Tosello, V., Mansour, M. R., Barnes, K., Paganin, M., Sulis, M. L., Jenkinson, S., ... Ferrando, A. A. (2009). WT1 mutations in T-ALL. Blood, 114(5), 1038-1045. https://doi.org/10.1182/blood-2008-12-192039

WT1 mutations in T-ALL. / Tosello, Valeria; Mansour, Marc R.; Barnes, Kelly; Paganin, Maddalena; Sulis, Maria Luisa; Jenkinson, Sarah; Allen, Christopher G.; Gale, Rosemary E.; Linch, David C.; Palomero, Teresa; Real, Pedro; Murty, Vundavalli; Yao, Xiaopan; Richards, Susan M.; Goldstone, Anthony; Rowe, Jacob; Basso, Giuseppe; Wiernik, Peter H.; Paietta, Elisabeth M.; Pieters, Rob; Horstmann, Martin; Meijerink, Jules P P; Ferrando, Adolfo A.

In: Blood, Vol. 114, No. 5, 2009, p. 1038-1045.

Research output: Contribution to journalArticle

Tosello, V, Mansour, MR, Barnes, K, Paganin, M, Sulis, ML, Jenkinson, S, Allen, CG, Gale, RE, Linch, DC, Palomero, T, Real, P, Murty, V, Yao, X, Richards, SM, Goldstone, A, Rowe, J, Basso, G, Wiernik, PH, Paietta, EM, Pieters, R, Horstmann, M, Meijerink, JPP & Ferrando, AA 2009, 'WT1 mutations in T-ALL', Blood, vol. 114, no. 5, pp. 1038-1045. https://doi.org/10.1182/blood-2008-12-192039
Tosello V, Mansour MR, Barnes K, Paganin M, Sulis ML, Jenkinson S et al. WT1 mutations in T-ALL. Blood. 2009;114(5):1038-1045. https://doi.org/10.1182/blood-2008-12-192039
Tosello, Valeria ; Mansour, Marc R. ; Barnes, Kelly ; Paganin, Maddalena ; Sulis, Maria Luisa ; Jenkinson, Sarah ; Allen, Christopher G. ; Gale, Rosemary E. ; Linch, David C. ; Palomero, Teresa ; Real, Pedro ; Murty, Vundavalli ; Yao, Xiaopan ; Richards, Susan M. ; Goldstone, Anthony ; Rowe, Jacob ; Basso, Giuseppe ; Wiernik, Peter H. ; Paietta, Elisabeth M. ; Pieters, Rob ; Horstmann, Martin ; Meijerink, Jules P P ; Ferrando, Adolfo A. / WT1 mutations in T-ALL. In: Blood. 2009 ; Vol. 114, No. 5. pp. 1038-1045.
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AU - Jenkinson, Sarah

AU - Allen, Christopher G.

AU - Gale, Rosemary E.

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AU - Palomero, Teresa

AU - Real, Pedro

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AU - Yao, Xiaopan

AU - Richards, Susan M.

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AU - Rowe, Jacob

AU - Basso, Giuseppe

AU - Wiernik, Peter H.

AU - Paietta, Elisabeth M.

AU - Pieters, Rob

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AU - Meijerink, Jules P P

AU - Ferrando, Adolfo A.

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