Blood: RUNX1 and CBF beta-SMMHC jointly trans-activate abnormal myelin ancestral cells to promote leukemia.

Chromosome 16 inverted is a consistent feature of M4 subtype acute myeloid leukemia in patients with eosinophil growth (AML M4Eo), which produces the CBFB-MYH11 fusion gene.
the fusion protein CBF beta-SMMHC, encoded by the CBFB-MYH11 fusion gene, is considered to be a significant negative inhibitor of RUNX1.
, however, recent studies challenge the RUNX1 inhibition model of leukemia mediated by CBF beta-SMMHC.
to clarify the role of Runx1 in CBFB-MYH11-induced leukemia, the researchers interbred mice with conditioned knock-out of the Runx1 gene (Runx1f/f) with conditional Cfb-MYH11 knock-in mice (Cbfb plus/56M).
Mx1-Cre, induced by Poly (I:C, pIpC) injection induced by poy (I:C, pIpC) after pIpC treatment, all leukemia occurred in Mx1-CreCbfb-plus/56M mice within 5 months, while Runx1f/fMx1-CreCbfb-plus/56M mice did not develop leukemia, and the effect was cellular.
pIpC treatment after different times AMP cells as a proportion of bone marrow cells is important, in Runx1f/fMx1-CreCbfb/56M mice, Cbfb-MYH11-induced leukemia starting cell group - abnormal myeloid ancestral cells (AMPs) decreased or even disappeared.
RNA-seq analysis of AMP cells showed that Mx1-CreCbfb-56M and Runx1f/fMx1-CreCbfb-56M mice had differential expressions associated with proliferation, differentiation blocking, and leukemia starting genes.
addition, by chromosomal immunocute sequencing (ChIC-seq), the researchers observed that the RUNX1/CBF beta-SMMHC target gene was significantly rich in Runx1f/fMx1-CreCbfb-56m cells, especially in the downgraded gene, suggesting that RUNX1 and CBF beta-SMMHC act together to activate gene expression primarily by directly binding the target gene.
above, this study shows that Runx1 is indispensable in the development of CBfb-MYH11-induced leukemia, and that it co-regulates key genes associated with the generation of functional AMP populations with CBF beta-SMMHC.
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