The role of the Wilms tumour gene (WT1) in normal and malignant haematopoiesis

Suzie Ariyaratana, David M. Loeb

Research output: Contribution to journalArticle

75 Citations (Scopus)

Abstract

In addition to its loss playing a pivotal role in the development of a childhood kidney malignancy, the Wilms tumour 1 gene (WT1) has emerged as an important factor in normal and malignant haematopoiesis. Preferentially expressed in CD34+ haematopoietic progenitors and down-regulated in more-differentiated cells, the WT1 transcription factor has been implicated in regulation of apoptosis, proliferation and differentiation. Putative target genes, such as BCL2, MYC, A1 and cyclin E, may cooperate with WT1 to modulate cell growth. However, the effects of WT1 on target gene expression appear to be isoform-specific. Certain WT1 isoforms are over-represented in leukaemia, but the exact mechanisms underlying the role of WT1 in transformation remain unclear. The ubiquity of WT1 in haematological malignancies has led to efforts to exploit it as a marker for minimal residual disease and as a prognostic factor, with conflicting results. In vitro killing of tumour cells by WT1-specific CD8+ cytotoxic T lymphocytes facilitated design of Phase I vaccine trials that showed clinical regression of WT1-positive tumours. Alternative methods employing WT1-specific immunotherapy are being investigated and might ultimately be used to optimise multimodal therapy of haematological malignancies.

Original languageEnglish (US)
Pages (from-to)1-17
Number of pages17
JournalExpert Reviews in Molecular Medicine
Volume9
Issue number14
DOIs
StatePublished - May 1 2007
Externally publishedYes

Fingerprint

Wilms' Tumor Genes
Wilms Tumor
Hematopoiesis
Tumors
Genes
Hematologic Neoplasms
Protein Isoforms
Cyclin E
Neoplasms
Residual Neoplasm
Cytotoxic T-Lymphocytes
T-cells
Immunotherapy
Cell growth
Leukemia
Gene expression
Transcription Factors
Vaccines

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)
  • Molecular Medicine

Cite this

The role of the Wilms tumour gene (WT1) in normal and malignant haematopoiesis. / Ariyaratana, Suzie; Loeb, David M.

In: Expert Reviews in Molecular Medicine, Vol. 9, No. 14, 01.05.2007, p. 1-17.

Research output: Contribution to journalArticle

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