STAT3b 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 Gyorffy, Heinz Sill, Florian Grebien, Richard Moriggl, Emilio Casanova, Dagmar Stoiber

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Signal transducer and activator of transcription 3 (STAT3) exists in 2 alternatively spliced isoforms, STAT3a and STAT3b. Although truncated STAT3b was originally postulated to act as a dominant-negative form of STAT3a, it has been shown to have various STAT3a-independent regulatory functions. Recently, STAT3b gained attention as a powerful antitumorigenic molecule in cancer. Deregulated STAT3 signaling is often found in acute myeloid leukemia (AML); however, the role of STAT3b in AML remains elusive. Therefore, we analyzed the STAT3b/a messenger RNA (mRNA) expression ratio in AML patients, where we observed that a higher STAT3b/a mRNA ratio correlated with a favorable prognosis and increased overall survival. To gain better understanding of the function of STAT3b in AML, we engineered a transgenic mouse allowing for balanced Stat3b expression. Transgenic Stat3b 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 STAT3b 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 STAT3b 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 - 2019

ASJC Scopus subject areas

  • Hematology

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    Aigner, P., Mizutani, T., Horvath, J., Eder, T., Heber, S., Lind, K., Just, V., Moll, H. P., Yeroslaviz, A., Fischer, M. J. M., Kenner, L., Gyorffy, B., Sill, H., Grebien, F., Moriggl, R., Casanova, E., & Stoiber, D. (2019). STAT3b is a tumor suppressor in acute myeloid leukemia. Blood Advances, 3(13), 1989-2002. https://doi.org/10.1182/bloodadvances.2018026385