Blood: The role of fusion transcription factor PML/RAR alpha in the progression of acute early granulocytic leukemia.

Central point: The direct target map of ML/RAR alpha redefines activation through super-enhancers and explains the synergy of ATRA/ATO;
: Transcription disorders caused by carcinogenic fusion proteins play a vital role in leukemia.
popular view is that the carcinogenic fusion protein PML/RAR alpha, produced by chromosomal transposing t (15;17), acts as a transcription inhibitor in acute early granulocytic leukemia (APL).
in this study, researchers provide rich evidence of how PML/RAR alpha drives tumor occurrence by inhibiting and activating two functions, in particular the importance of newly discovered activation in the development of leukemia in APL.
the activation function of PML/RAR alpha is achieved by collecting large amounts of P300 and HDAC1 and forming super enhancers.
two drugs widely used in APL therapy, all-trans methicilloric acid and arsenic trioxide, act as synergies in APL cells to regulate PML/RAR alpha regulatory targets associated with super-enhancers.
researchers used a series of in vitro and in vivo experiments to demonstrate that the PML/RAR alpha-active target gene GFI1 is necessary for the maintenance of APL cells, and that PML/RAR alpha may be lowly polymerized, infesting GFI1 by chromatin configuration in the super-enhancer region.
, the researchers analyzed the targets of GFI1 and revealed that GFI1 and PML/RAR alpha co-regulate the interaction of target genes in chromatin.
, the study expounds the dual role of fusion transcription factors in driving leukemia progression in transcription disorder, and emphasizes the importance of the overall analytical regulatory circuit.
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