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Leukemia associated mutant Wilms' tumor gene 1 protein promotes expansion of human hematopoietic progenitor cells.

Vidovic, Karina LU ; Ullmark, Tove LU ; Rosberg, Bodil LU ; Lennartsson, Andreas LU ; Olofsson, Tor LU ; Nilsson, Björn LU and Gullberg, Urban LU (2013) In Leukemia Research: A Forum for Studies on Leukemia and Normal Hemopoiesis 37(10). p.1341-1349
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,... (More)
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. (Less)
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Contribution to journal
publication status
published
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in
Leukemia Research: A Forum for Studies on Leukemia and Normal Hemopoiesis
volume
37
issue
10
pages
1341 - 1349
publisher
Elsevier
external identifiers
  • wos:000324099100028
  • pmid:23871158
  • scopus:84883557198
  • pmid:23871158
ISSN
1873-5835
DOI
10.1016/j.leukres.2013.06.018
language
English
LU publication?
yes
id
ada5eb33-e2b4-42f6-8b07-684dc7c14767 (old id 3955732)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/23871158?dopt=Abstract
date added to LUP
2016-04-01 09:54:52
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2020-01-05 03:38:10
@article{ada5eb33-e2b4-42f6-8b07-684dc7c14767,
  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.},
  author       = {Vidovic, Karina and Ullmark, Tove and Rosberg, Bodil and Lennartsson, Andreas and Olofsson, Tor and Nilsson, Björn and Gullberg, Urban},
  issn         = {1873-5835},
  language     = {eng},
  number       = {10},
  pages        = {1341--1349},
  publisher    = {Elsevier},
  series       = {Leukemia Research: A Forum for Studies on Leukemia and Normal Hemopoiesis},
  title        = {Leukemia associated mutant Wilms' tumor gene 1 protein promotes expansion of human hematopoietic progenitor cells.},
  url          = {https://lup.lub.lu.se/search/ws/files/1383913/4173655.pdf},
  doi          = {10.1016/j.leukres.2013.06.018},
  volume       = {37},
  year         = {2013},
}