Analysis of mutational status, SNP rs16754, and expression levels of Wilms tumor 1 (WT1) gene in acute promyelocytic leukemia

Girish Chander Gaur, Safaa M. Ramadan, Laura Cicconi, Nélida I. Noguera, Irene Luna, Esperanza Such, Serena Lavorgna, Jonny Di Giandomenico, Miguel A. Sanz, Francesco Lo-Coco

Research output: Contribution to journalArticle

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Abstract

Overexpression, polymorphisms, and mutations of the WT1 gene have been reported in several human tumors including acute myeloid leukemia (AML) and variably correlated with prognosis. Acute promyelocytic leukemia (APL) represents the AML subset disclosing higher WT1 expression levels; however, no WT1 studies specifically focused on APL have been conducted. We screened for the presence of mutations, SNP rs16754, and expression levels of WT1 gene in 103 adult patients with newly diagnosed APL. Fms-like tyrosine kinase (FLT3) mutations were analyzed as well. WT1 mutations were identified in four (4 %) patients. At least one copy of the minor SNP rs16754 allele (WT1AG or WT1GG) was detected in 30 (29 %) patients. Six patients (6 %) were homozygous for the minor allele (WT1GG) and this genotype was associated with higher WT1 mRNA copies (p=0.018). FLT3 mutations were found in 37 % of patients and correlated with high WT1 mRNA expression (p=0.004). Patients heterozygous or homozygous for the minor allele and patients homozygous for major (WT1AA) allele did not differ in terms of presenting features. In adult APL, WT1 gene mutational and polymorphic profile shows similarities with pediatric AML rather than with adult AML.

Original languageEnglish
Pages (from-to)1855-1860
Number of pages6
JournalAnnals of Hematology
Volume91
Issue number12
DOIs
Publication statusPublished - Dec 2012

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Wilms' Tumor Genes
Acute Promyelocytic Leukemia
Wilms Tumor
Single Nucleotide Polymorphism
Acute Myeloid Leukemia
Mutation
Alleles
Vascular Endothelial Growth Factor Receptor-1
Messenger RNA
Genotype
Pediatrics

Keywords

  • Acute promyelocytic leukemia
  • FLT3
  • SNP rs16754
  • Wilms tumor 1
  • WT1 copy number

ASJC Scopus subject areas

  • Hematology

Cite this

Analysis of mutational status, SNP rs16754, and expression levels of Wilms tumor 1 (WT1) gene in acute promyelocytic leukemia. / Gaur, Girish Chander; Ramadan, Safaa M.; Cicconi, Laura; Noguera, Nélida I.; Luna, Irene; Such, Esperanza; Lavorgna, Serena; Di Giandomenico, Jonny; Sanz, Miguel A.; Lo-Coco, Francesco.

In: Annals of Hematology, Vol. 91, No. 12, 12.2012, p. 1855-1860.

Research output: Contribution to journalArticle

Gaur, Girish Chander ; Ramadan, Safaa M. ; Cicconi, Laura ; Noguera, Nélida I. ; Luna, Irene ; Such, Esperanza ; Lavorgna, Serena ; Di Giandomenico, Jonny ; Sanz, Miguel A. ; Lo-Coco, Francesco. / Analysis of mutational status, SNP rs16754, and expression levels of Wilms tumor 1 (WT1) gene in acute promyelocytic leukemia. In: Annals of Hematology. 2012 ; Vol. 91, No. 12. pp. 1855-1860.
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