Homoharringtonine deregulates MYC transcriptional expression by directly binding NF-κB repressing factor.

ABSTRACT: Homoharringtonine (HHT), a known protein synthesis inhibitor, has an anti-myeloid leukemia effect and potentiates the therapeutic efficacy of anthracycline/cytarabine induction regimens for acute myelogenous leukemia (AML) with favorable and intermediate prognoses, especially in the t(8;21) subtype. Here we provide evidence showing that HHT inhibits the activity of leukemia-initiating cells (Lin^-/Sca-1^-/c-kit⁺; LICs) in a t(8;21) murine leukemia model and exerts a down-regulating effect on MYC pathway genes in human t(8;21) leukemia cells (Kasumi-1). We discovered that NF-κB repressing factor (NKRF) is bound directly by HHT via the second double-strand RNA-binding motif (DSRM2) domain, which is the nuclear localization signal of NKRF. A series of deletion a

SUBMITTER: Chen XJ 

PROVIDER: S-EPMC6369765 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature