Installation of a cancer promoting WNT/SIX1 signaling axis by the oncofusion protein MLL-AF9.

ABSTRACT:

Background

Chromosomal translocation-induced expression of the chromatin modifying oncofusion protein MLL-AF9 promotes acute myelocytic leukemia (AML). Whereas WNT/β-catenin signaling has previously been shown to support MLL-AF9-driven leukemogenesis, the mechanism underlying this relationship remains unclear.

Methods

We used two novel small molecules targeting WNT signaling as well as a genetically modified mouse model that allow targeted deletion of the WNT protein chaperone Wntless (WLS) to evaluate the role of WNT signaling in AML progression. ATAC-seq and transcriptome profiling were deployed to understand the cellular consequences of disrupting a WNT signaling in leukemic initiating cells (LICs).

Findings

We identified Six1 to be a WNT-controlled target gene in

SUBMITTER: Zhang LS 

PROVIDER: S-EPMC6354558 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature