Leukemia associated mutant Wilms' tumor gene 1 protein promotes expansion of human hematopoietic progenitor cells.
Author
Summary, in English
The transcription factor Wilms' tumor gene 1 (WT1) is highly expressed in the majority of leukemias, suggesting a role in leukemogenesis. Acquired WT1 mutations are reported as an independent predictor of poor clinical outcome, and mutations resulting in deletion of the entire DNA-binding zinc-finger domain (WT1delZ), is the most common type. The aim of this study was to study cellular effects of WT1(delZ) that may contribute to an oncogenic phenotype. We found that expression of WT1(delZ) supported proliferation of human hematopoietic CD34(+) progenitor cells. Moreover, WT1(delZ) transduced cells expressed erythroid markers, including raised levels of STAT5, independently of addition of erythropoietin. At the global gene expression level, WT1(delZ) caused upregulation of genes related to cell division and genes associated with erythroid maturation, in the absence of added erythropoietin. Our results indicate that WT1(delZ) promotes cell proliferation and expansion of progenitor cells, consistent with a possible role in leukemogenesis.
Department/s
- Division of Hematology and Transfusion Medicine
- Transcriptional mechanisms for the Wilms’ tumor gene 1 (WT1) oncoprotein
- BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
Publishing year
2013
Language
English
Pages
1341-1349
Publication/Series
Leukemia Research: A Forum for Studies on Leukemia and Normal Hemopoiesis
Volume
37
Issue
10
Full text
Links
Document type
Journal article
Publisher
Elsevier
Topic
- Cancer and Oncology
Status
Published
Research group
- Transcriptional mechanisms for the Wilms’ tumor gene 1 (WT1) oncoprotein
ISBN/ISSN/Other
- ISSN: 1873-5835