Three-Dimensional Genome Organization Maps In Normal Haematopoietic Stem Cells And Acute Myeloid Leukemia.

Acute Myeloid Leukemia (AML) is a highly lethal blood cancer arising due to aberrant differentiation of haematopoietic stem cells. and regulate stemness-related transcriptional programs in normal haematopoietic stem cells and AML. Here we obtained 3D genome organization maps in the CD34+ haematopoietic stem cells from 3 healthy individuals and 3 individuals with AML. The oncogenic transcription factor is regulated by a Frequently Interacting Region (FIRE). This FIRE is present in normal bone marrow samples, and an AML sample with high levels. However, it is absent in two AML samples that show low levels. CRISPR excision of the FIRE led to loss of and reduced cell growth. Moreover, MEIS1 can bind to the promoter of , and HOXA9 can also auto-regulate by binding to its own promoter as well as an Acute Myeloid Leukemia-specific super-enhancer that interacts with the promoter via chromatin interactions.