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STAT3β is a tumor suppressor in acute myeloid leukemia

2019; Elsevier BV; Volume: 3; Issue: 13 Linguagem: Inglês

10.1182/bloodadvances.2018026385

2473-9537

Petra Aigner, Tatsuaki Mizutani, Jaqueline Horvath, Thomas Eder, Stefan Heber, K. 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,

Myeloproliferative Neoplasms: Diagnosis and Treatment

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.