STAT3β is a tumor suppressor in acute myeloid leukemia

Petra Aigner, Tatsuaki Mizutani, Jaqueline Horvath, Thomas Eder, Stefan Heber, Karin Lind, Valentin Just, Herwig P Moll, Assa Yeroslaviz, Michael J M Fischer, Lukas Kenner, Balázs Győrffy, Heinz Sill, Florian Grebien, Richard Moriggl, Emilio Casanova, Dagmar Stoiber

Research output: Journal article (peer-reviewed)Journal article

10 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1989-2002
Number of pages14
JournalBlood advances
Volume3
Issue number13
DOIs
Publication statusPublished - 9 Jul 2019

Keywords

  • Animals
  • Biomarkers
  • Biopsy
  • Cell Line
  • Disease Models, Animal
  • Disease Susceptibility
  • Gene Expression Profiling
  • Gene Expression Regulation, Leukemic
  • Humans
  • Immunohistochemistry
  • Leukemia, Myeloid, Acute/diagnosis
  • Mice
  • Prognosis
  • STAT3 Transcription Factor/genetics
  • Tumor Suppressor Proteins/genetics

ASJC Scopus subject areas

  • Hematology

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