PSPC1 selectively controls tumorigenesis and oncogenic transcription in acute myeloid leukemia [ChIP-seq]

Acute myeloid leukemia (AML) is an aggressive hematopoietic malignancy characterized by the blockage of myeloid cell differentiation and uncontrolled proliferation of immature myeloid cells. Here, we show that paraspeckle component 1 (PSPC1) is aberrantly overexpressed in AML and high level of PSPC1 expression is associated with poor survival in AML patients. We demonstrate that PSPC1 loss dramatically suppresses leukemia maintenance and initiation/development as well as self-renewal of leukemia stem cells (LSCs) but has no effect on normal hematopoiesis. Mechanistically, PSPC1 interacts with PU.1, and they co-occupy the chromatin, especially at promoter regions proximal to transcription start site (TSS). Recruitment of PSPC1 and PU.1 on co-bound regions was dependent on each other to regulate target genes expression such as NDC1, a prognostic marker in multiple tumors. Collectively, our findings uncover a selective and crucial role of PSPC1 in AML and highlight its potential as a promising therapeutic target for myeloid malignancies. Overall design: ChIP-seq for OCIAML5 with IgG, PSPC1 or PU.1 antibody to identify the genome occupancy of PSPC1 and PU.1.