STAT3? is a tumor suppressor in acute myeloid leukemia.

ABSTRACT: Signal transducer and activator of transcription 3 (STAT3) exists in 2 alternatively spliced isoforms, STAT3? and STAT3?. Although truncated STAT3? was originally postulated to act as a dominant-negative form of STAT3?, it has been shown to have various STAT3?-independent regulatory functions. Recently, STAT3? gained attention as a powerful antitumorigenic molecule in cancer. Deregulated STAT3 signaling is often found in acute myeloid leukemia (AML); however, the role of STAT3? in AML remains elusive. Therefore, we analyzed the STAT3?/? messenger RNA (mRNA) expression ratio in AML patients, where we observed that a higher STAT3?/? mRNA ratio correlated with a favorable prognosis and increased overall survival. To gain better understanding of the function of STAT3? in AML, we engineered a transgenic mouse allowing for balanced Stat3? expression. Transgenic Stat3? 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 STAT3? 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 STAT3? plays an essential tumor-suppressive role in AML.

SUBMITTER: Aigner P 

PROVIDER: S-EPMC6616266 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature