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  STAT3 beta is a tumor suppressor in acute myeloid leukemia

Aigner, P., Mizutani, T., Horvath, J., Eder, T., Heber, S., Lind, K., et al. (2019). STAT3 beta is a tumor suppressor in acute myeloid leukemia. Blood Advances, 3(13), 1989-2002. doi:10.1182/bloodadvances.2018026385.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0004-814B-6 Version Permalink: http://hdl.handle.net/21.11116/0000-0004-814C-5
Genre: Journal Article

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 Creators:
Aigner, Petra1, Author
Mizutani, Tatsuaki1, Author
Horvath, Jaqueline1, Author
Eder, Thomas1, Author
Heber, Stefan1, Author
Lind, Karin1, Author
Just, Valentin1, Author
Moll, Herwig P.1, Author
Yeroslaviz, Assa2, Author              
Fischer, Michael J. M.1, Author
Kenner, Lukas1, Author
Gyorffy, Balazs1, Author
Sill, Heinz1, Author
Grebient, Florian1, Author
Moriggl, Richard1, Author
Casanova, Emilio1, Author
Stoiber, Dagmar1, Author
Affiliations:
1external, ou_persistent22              
2Habermann, Bianca / Computational Biology, Max Planck Institute of Biochemistry, Max Planck Society, ou_1832284              

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Free keywords: HEMATOPOIETIC STEM-CELLS; ACUTE MYELOGENOUS LEUKEMIA; ADHESION MOLECULES; L-SELECTIN; MULTIPLE CYTOKINES; SIGNAL TRANSDUCER; NUCLEAR RETENTION; STAT5 ACTIVATION; SERUM-LEVELS; EXPRESSIONHematology;
 Abstract: Signal transducer and activator of transcription 3 (STAT3) exists in 2 alternatively spliced isoforms, STAT3 alpha and STAT3 beta. Although truncated STAT3 beta was originally postulated to act as a dominant-negative form of STAT3 alpha, it has been shown to have various STAT3 alpha-aindependent regulatory functions. Recently, STAT3 beta gained attention as a powerful antitumorigenic molecule in cancer. Deregulated STAT3 signaling is often found in acute myeloid leukemia (AML); however, the role of STAT3 beta in AML remains elusive. Therefore, we analyzed the STAT3 beta/alpha messenger RNA (mRNA) expression ratio in AML patients, where we observed that a higher STAT3 beta/alpha mRNA ratio correlated with a favorable prognosis and increased overall survival. To gain better understanding of the function of STAT3 beta in AML, we engineered a transgenic mouse allowing for balanced Stat3 beta expression. Transgenic Stat3 beta expression resulted in decelerated disease progression and extended survival in PTEN- and MLL-AF9-dependent AML mouse models. Our findings further suggest that the antitumorigenic function of STAT3 beta depends on the tumor-intrinsic regulation of a small set of significantly up- and downregulated genes, identified via RNA sequencing. In conclusion, we demonstrate that STAT3 beta plays an essential tumor-suppressive role in AML.

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Language(s): eng - English
 Dates: 2019
 Publication Status: Published in print
 Pages: 14
 Publishing info: -
 Table of Contents: -
 Rev. Method: -
 Degree: -

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Title: Blood Advances
Source Genre: Journal
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Publ. Info: 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA : AMER SOC HEMATOLOGY
Pages: - Volume / Issue: 3 (13) Sequence Number: - Start / End Page: 1989 - 2002 Identifier: ISSN: 2473-9529