Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:2.1.1.37 (
DNA methyltransferase
)
4,983
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The AML1-ETO fusion protein (A/E), which results from the t(8;21) translocation, is considered to be a leukemia-initiating event. Identifying the mechanisms underlying the oncogenic activity of A/E remains a major challenge. In this study, we identified a specific down-regulation of
brain acid-soluble protein 1
(
BASP1
) in t(8;21) acute myeloid leukemia (AML). A/E recognized AML1-binding sites and recruited
DNA methyltransferase
3a (DNMT3a) to the
BASP1
promoter sequence, which triggered DNA methylation-mediated silencing of
BASP1
. Ectopic expression of
BASP1
inhibited proliferation and the colony-forming ability of A/E-positive AML cell lines and led to apoptosis and cell cycle arrest. The DNMT inhibitor decitabine up-regulated the expression of
BASP1
in A/E-positive AML cell lines. In conclusion, our data suggest that
BASP1
silencing via promoter methylation may be involved in A/E-mediated leukemogenesis and that
BASP1
targeting may be an actionable therapeutic strategy in t(8;21) AML.
...
PMID:Methylation-associated silencing of BASP1 contributes to leukemogenesis in t(8;21) acute myeloid leukemia. 2967 93
