Blood: Trib1 promotes AML progress by adjusting the transcription of Hoxa9.

Center point: Trib1 can affect Hoxa9 in myeloid leukemia by degrading C/EBP alpha and modifying Hoxa9-related super-enhancers; Erg is a key target for Trib1 and Hoxa9, responds to BRD4 inhibition, and plays a key role in leukemia.
abstract: The prosthetic kinase Trib1 acts as a myelin-like cancer gene, collecting E3 Ubivirin densin COP1 on C/EBPa and interacting with MEK1 to enhance ERK phosphorylation.
the close genetic effects of Trib1 on Hoxa9 have been observed in the course of myeloid leukemia, where trib1 over-expression can significantly accelerate the occurrence of Hoxa9-induced leukemia.
but how Trib1 functionally regulates Hoxa9 transcription activity is unclear.
in this study, Yoshino and others confirmed that Trib1 regulates super-enhancers associated with Hoxa9.
ChIP-seq analysis showed that the histrotein H3K27Ac signals at the super-enhancers of the Erg, Spns2, Rgl1, and Pyk3cd gene constellations were enhanced, with increased mRNA expression of these genes.
modification of the super-enhancer activity is mainly achieved through Trib1 degradation C/EBPa p42, while the MEK/ERK path contributes less.
silent Erg eliminates the growth advantage gained by Trib1 over-expression, indicating that Erg is a key downstream target for the Trib1/Hoxa9 axis.
addition, the treatment of acute myeloid leukemia (AML) cells with BRD4 inhibitor JQ1 showed Trib1/Erg-dependent growth inhibition both in vitro and in vivo.
ERG increase caused by TRIB1 has also been observed in human AML cell line, suggesting that Trib1 is a potential therapeutic target for Hoxa9-related AML.
, the study reveals a new mechanism by which Trib1 regulates chromosate and Hoxa9-driven transcription during myeloid leukemia.
.