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Methylation-associated silencing of BASP1 contributes to leukemogenesis in t(8;21) acute myeloid leukemia.


ABSTRACT: 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.

SUBMITTER: Zhou L 

PROVIDER: S-EPMC5938046 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Methylation-associated silencing of BASP1 contributes to leukemogenesis in t(8;21) acute myeloid leukemia.

Zhou Lei L   Fu Lin L   Lv Na N   Liu Jing J   Li Yan Y   Chen Xiaosu X   Xu Qingyu Q   Chen Guofeng G   Pang Baoxu B   Wang Lili L   Li Yonghui Y   Zhang Xiaodong X   Yu Li L  

Experimental & molecular medicine 20180420 4


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 meth  ...[more]

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