Transcriptional circuits that regulate early T cell precursor acute leukemia [Hi-C]
The discovery of early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) was based on expression of stem cell genes that are characteristic of mouse ETP cells, the most primitive multipotent cells in the thymus. Using complementary mouse and human genetic models and genome-wide expression and chromatin profiling integrated with 3D chromatin mapping, we show that the PIAS-like coactivator ZMIZ1 promotes immature T-ALL proliferation by recruiting the transcription factor MYB in feedforward circuits to cooperatively induce MYCN, MEF2C, and BCL2, which were recently associated with the high-risk bone marrow progenitor (BMP-like) subset. Overall design: Mouse bone marrow-derived hematopoietic stem and progenitor cells (Lin-Sca+Kit+) were collected and analyzed for 3D chromatin structure.