A novel function of STAT3β in suppressing interferon response improves outcome in acute myeloid leukemia

To elucidate the role of STAT3β in acute myeloid leukemia (AML), we established a mouse model of STAT3β-deficient, MLL-AF9-driven AML. STAT3β-deficiency significantly shortened survival of leukemic mice confirming its role as a tumor suppressor. Furthermore, RNA sequencing revealed enhanced STAT1 expression and interferon (IFN) signaling upon loss of STAT3β. To investigate the differences in gene expression in STAT3β expressing and deficient leukemia cells, MLL-AF9-transformed fetal liver cells were generated and transplanted into immunocompromised mice. Leukemic blasts were isolated from bone marrow (n=3 per group) and spleen (n=3 per group) of diseased animals by sorting Venus+ cells using a BD FACSymphonyTM S6 Cell Sorter (BD Bioscience) and subjected to RNA sequencing.