Leukemia associated mutant Wilms' tumor gene 1 protein promotes expansion of human hematopoietic progenitor cells.
Författare
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.
Avdelning/ar
- Avdelningen för hematologi och transfusionsmedicin
- Undersökning av molekylära sjukdomsmekanismer vid blodcancer
- BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
Publiceringsår
2013
Språk
Engelska
Sidor
1341-1349
Publikation/Tidskrift/Serie
Leukemia Research: A Forum for Studies on Leukemia and Normal Hemopoiesis
Volym
37
Issue
10
Fulltext
Länkar
Dokumenttyp
Artikel i tidskrift
Förlag
Elsevier
Ämne
- Cancer and Oncology
Status
Published
Forskningsgrupp
- Transcriptional mechanisms for the Wilms’ tumor gene 1 (WT1) oncoprotein
ISBN/ISSN/Övrigt
- ISSN: 1873-5835