A novel AML1-ETO/FTO positive feedback loop promotes leukemogenesis and Ara-C resistance via stabilizing IGFBP2 in t(8;21) acute myeloid leukemia.

ABSTRACT:

Background

t(8;21)(q22;q22) is one of the most frequent chromosomal abnormalities in acute myeloid leukemia (AML), leading to the generation of the fusion protein AML1-ETO. Despite t(8;21) AML being considered as a subtype with a favorable prognosis, approximately 30-50% of patients experience drug resistance and subsequent relapse. N⁶-methyladenosine (m⁶A) is demonstrated to be involved in the development of AML. However, the regulatory mechanisms between AML1-ETO and m⁶A-related enzymes and the roles of dysregulated m⁶A modifications in the t(8;21)-leukemogenesis and chemoresistance remain elusive.

Methods

Chromatin immunoprecipitation, dual-luciferase reporter assay, m⁶A-qPCR, RNA immunoprecipitation, and RNA stabilit

SUBMITTER: Zhou W 

PROVIDER: S-EPMC10807068 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature