STAT3β is a tumor suppressor in acute myeloid leukemia

Signal transducer and activator of transcription 3 (STAT3), an important multifunctional regulator of transcription, is expressed in two alternatively spliced isoforms, STAT3α and truncated STAT3β. While STAT3β was 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 anti-tumorigenic molecule in cancer. Deregulated STAT3 signaling is frequently observed in hematological malignancies, however, the role of STAT3β in acute myeloid leukemia (AML) remains elusive. We analyzed a cohort of AML patients for the STAT3β/α mRNA expression ratio and observed that a higher STAT3β/α ratio correlated with a favorable prognosis and increased overall survival. To gain better understanding of the function of STAT3β in leukemia we engineered a transgenic mouse allowing for balanced Stat3β expression. Transgenic Stat3β expression resulted in enhanced disease latency in PTEN- and MLL-AF9-dependent mouse models of AML. In conclusion, we demonstrate that STAT3β plays an essential tumor suppressor role in AML and its mRNA expression acts as an important prognostic tool in AML patients. RNA-seq of sorted Venus + BM cells ( Stat3β TG ) and wt, 3 replicates each