Constitutive expression of the wilms' tumor gene (wt1) in the leukemic cell line u937 blocks parts of the differentiation program

ABSTRACT The Wilms tumor gene, WT1, encodes a zinc-finger DNA binding protein which is thought to function as a tissue specific transcription factor, regulating cell growth and

differentiation. High expression of WT1 has been detected in a range of acute leukemias. To elucidate a role for WT1 in leukemogenesis, we transfected the monoblastic cell line U937, which

lacks detectable levels of endogenous WT1, with two isoforms of WT1. We showed that, in contrast to U937 control cells, cells constitutively expressing either of the isoforms, WT1(−KTS) or

WT1(+KTS), did not respond to differentiation induction by retinoic acid or vitamin D3, as judged by the capacity to reduce nitro blue tetrazolium and morphology. Although U937 cells

expressing WT1 were hampered in their ability to differentiate on incubation with retinoic acid and vitamin D3, the induced G1/G0-accumulation was similar to differentiating control cells

treated with inducers. Furthermore, distinct effects on the maturation process were indicated by downregulation of the myeloid cell surface makers CD13 and CD15, while the upregulation of

CD14 and CD11c on WT1 transfected cells was similar to control cells upon incubation with retinoic acid and vitamin D3. Taken together our results demonstrate that a constitutive expression

of WT1 in the leukemic cell line U937 leads to impairment of differentiation responses, indicating that a high expression of WT1 can contribute to the differentiation block of acute

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INVOLVE TGF-Β AND NF-ΚB SIGNALING Article Open access 14 December 2021 AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Hematology, University of Lund, Lund, S-221 85, Sweden

Helena Svedberg, Kristina Chylicki & Urban Gullberg * Department of Oncology, University of Lund, Lund, S-221 85, Sweden Bo Baldetorp * The Wistar Institute, Philadelphia, 19104,

Pennsylvania, USA Frank J Rauscher III Authors * Helena Svedberg View author publications You can also search for this author inPubMed Google Scholar * Kristina Chylicki View author

publications You can also search for this author inPubMed Google Scholar * Bo Baldetorp View author publications You can also search for this author inPubMed Google Scholar * Frank J

Rauscher III View author publications You can also search for this author inPubMed Google Scholar * Urban Gullberg View author publications You can also search for this author inPubMed 

Google Scholar RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Svedberg, H., Chylicki, K., Baldetorp, B. _et al._ Constitutive expression of the

Wilms' tumor gene (WT1) in the leukemic cell line U937 blocks parts of the differentiation program. _Oncogene_ 16, 925–932 (1998). https://doi.org/10.1038/sj.onc.1201613 Download

citation * Received: 18 June 1997 * Accepted: 30 September 1997 * Published: 03 March 1998 * Issue Date: 19 February 1998 * DOI: https://doi.org/10.1038/sj.onc.1201613 SHARE THIS ARTICLE

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by the Springer Nature SharedIt content-sharing initiative KEYWORDS * WT1 * leukemia * differentiation * hematopoiesis * U937