Jurnal Internasional PRDM16s mentransformasikan progenitor megakaryocyte-erythroid menjadi sel yang memicu leukemia myeloid
Oncogenic mutations give cells the ability to propagate indefinitely, but whether oncogenes change the fate of these cells is unknown. Here, we show that the transcription regulator PRDM16s causes conversion of oncogenic fate by converting cells destined to form platelets and erythrocytes to myeloid leukemia stem cells (LSCs). Prdm16 expression in the megakaryocyte-erythroid progenitor (MEPs), which usually does not have the potential to produce granulomonocytic cells, causes AML by converting MEP to LSC. Prdm16s blocks the potential of megakaryocytic / erythroid by interacting with super enhancers and activating the myeloid master regulator, including PU.1. A CRISPR broken screen confirms that PU.1 is needed for Prdm16s induced leukemia. Ablating PU.1 weakens leukemogenesis and restores the potential megakaryocytic / erythroid MEP leukemia in mouse and human AML models by resetting PRDM16 . Thus, the oncogenic expression PRDM16 gave MPs the fate of LSC by activating the myeloid gene regulatory network.