Functions of BMI-1 in human leukemia cells. Homo sapiens

In this study, we aim to identify the functions of BMI-1 in human leukemias. Paired-end RNA-Seq and ChIP-Seq approaches were performed in BMI-1 over-expressed SEM cells. Integrative analysis found that BMI1 over-expression de-regulated JAK-STAT signaling through the induction of SOCS genes. It is probably due to the global depletion of PRC1-depositied H2AK119ub repressive mark. Clinically, we validated that patient-derived AML leukemia cells with higher BMI-1 expression was more sensitive to ruxolitinib treatment in vitro. Together, our results highlight a novel BMI-1-mediated JAK-STAT signaling pathway that negatively regulates survival of leukemia cells.