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Type of publication: Journal Article
Type of document: Full Paper

Year: 2019

Authors: Aigner, P; Mizutani, T; Horvath, J; Eder, T; Heber, S; Lind, K; Just, V; Moll, HP; Yeroslaviz, A; Fischer, MJM; Kenner, L; Győrffy, B; Sill, H; Grebien, F; Moriggl, R; Casanova, E; Stoiber, D

Title: STAT3β is a tumor suppressor in acute myeloid leukemia.

Source: Blood Adv. 2019; 3(13):1989-2002



Authors Vetmeduni Vienna:

Eder Thomas
Grebien Florian
Kenner Lukas
Moriggl Richard

Vetmed Research Units
Institute for Medical Biochemistry
Institute of Pathology, Pathology of Laboratory Animals
Institute of Animal Breeding and Genetics, Unit for Functional Cancer Genomics


Abstract:
Signal transducer and activator of transcription 3 (STAT3) exists in 2 alternatively spliced isoforms, STAT3α and STAT3β. Although truncated STAT3β was originally postulated to act as a dominant-negative form of STAT3α, it has been shown to have various STAT3α-independent regulatory functions. Recently, STAT3β gained attention as a powerful antitumorigenic molecule in cancer. Deregulated STAT3 signaling is often found in acute myeloid leukemia (AML); however, the role of STAT3β in AML remains elusive. Therefore, we analyzed the STAT3β/α messenger RNA (mRNA) expression ratio in AML patients, where we observed that a higher STAT3β/α mRNA ratio correlated with a favorable prognosis and increased overall survival. To gain better understanding of the function of STAT3β in AML, we engineered a transgenic mouse allowing for balanced Stat3β expression. Transgenic Stat3β 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 STAT3β 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 STAT3β plays an essential tumor-suppressive role in AML.© 2019 by The American Society of Hematology.

Keywords Pubmed: Animals
Biomarkers
Biopsy
Cell Line
Disease Models, Animal
Disease Susceptibility
Gene Expression Profiling
Gene Expression Regulation, Leukemic
Humans
Immunohistochemistry
Leukemia, Myeloid, Acutediagnosisetiologymetabolismmortality
Mice
Prognosis
STAT3 Transcription Factorgeneticsmetabolism
Tumor Suppressor Proteinsgeneticsmetabolism

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