Unknown,Transcriptomics,Genomics,Proteomics

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Genome-wide studies identify a novel interplay between AML1 and AML1/ETO in t(8;21) acute myeloid leukemia


ABSTRACT: The AML1/ETO fusion protein is essential to the development of acute myeloid leukemia (AML), and is well recognized for its dominant-negative effect on the co-existing wild-type protein AML1. However, the involvement of wild-type AML1 in AML1/ETO-driven leukemogenesis remains elusive. Through chromatin immunoprecipitation sequencing, computational analysis plus a series of experimental validations, we report here that AML1 is able to orchestrate the expression of AML1/ETO targets regardless of being activated or repressed, via forming a complex with AML1/ETO and via recruiting the cofactor. 4 ChIP-seq assays were used to identify the high confidence binding regions of AML1-ETO and AML1 in t(8;21) AML Kasumi-1 cell lines. The anti-AML1 (N20) antibody targets the N-terminus of AML1 and recognizes both AML1 and AML1/ETO; the anti-AML1 (C19) antibody targets the C-terminus of AML1 and recognizes AML1 but not AML1/ETO; the anti-ETO (C20) antibody targets the C-terminus of ETO and specifically recognizes AML1/ETO. 2 ChIP-seq assays were used to identify the binding regions of AML1 in human macrophage U937 cell lines. And the total input was used as control.

ORGANISM(S): Homo sapiens

SUBMITTER: Huanwei Wang 

PROVIDER: E-GEOD-65427 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Genome-wide studies identify a novel interplay between AML1 and AML1/ETO in t(8;21) acute myeloid leukemia.

Li Yizhen Y   Wang Huanwei H   Wang Xiaoling X   Jin Wen W   Tan Yun Y   Fang Hai H   Chen Saijuan S   Chen Zhu Z   Wang Kankan K  

Blood 20151106 2


The AML1/ETO fusion protein is essential to the development of t(8;21) acute myeloid leukemia (AML) and is well recognized for its dominant-negative effect on the coexisting wild-type protein AML1. However, the genome-wide interplay between AML1/ETO and wild-type AML1 remains elusive in the leukemogenesis of t(8;21) AML. Through chromatin immunoprecipitation sequencing and computational analysis, followed by a series of experimental validations, we report here that wild-type AML1 is able to orch  ...[more]

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