title: Leukemia associated mutant Wilms' tumor gene 1 protein promotes expansion of human hematopoietic progenitor cells.
abstract: 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.
authors.affiliation: Division of Hematology and Transfusion Medicine, Lund University, Lund, Sweden. karina.vidovic@med.lu.se
authors.forename: Karina
authors.initials: K
authors.lastname: Vidovic
authors.forename: Tove
authors.initials: T
authors.lastname: Ullmark
authors.forename: Bodil
authors.initials: B
authors.lastname: Rosberg
authors.forename: Andreas
authors.initials: A
authors.lastname: Lennartsson
authors.forename: Tor
authors.initials: T
authors.lastname: Olofsson
authors.forename: Björn
authors.initials: B
authors.lastname: Nilsson
authors.forename: Urban
authors.initials: U
authors.lastname: Gullberg
mesh_terms: D018952:Antigens, CD34 / Q000378:metabolism; D018929:Cell Culture Techniques; D049109:Cell Proliferation; D003114:Colony-Forming Units Assay; D004921:Erythropoietin / Q000378:metabolism; D015870:Gene Expression; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D006441:Hemoglobin A / Q000378:metabolism; D006801:Humans; D007938:Leukemia / Q000235:genetics* / Q000378:metabolism*; D050505:Mutant Proteins; D050799:STAT5 Transcription Factor / Q000378:metabolism; D014161:Transduction, Genetic; D025721:WT1 Proteins / Q000235:genetics* / Q000378:metabolism*
chemical_list: D018952:Antigens, CD34; D050505:Mutant Proteins; D050799:STAT5 Transcription Factor; D025721:WT1 Proteins; D004921:Erythropoietin; D006441:Hemoglobin A
keywords: Leukemia; Progenitor cells; Proliferation WT1-mutant; STAT5