Overexpression of MN1 confers resistance to chemotherapy, accelerates leukemia onset, and suppresses p53 and Bim induction.

ABSTRACT:

Background

The transcriptional co-activator MN1 confers a worse prognosis for patients with acute myeloid leukemia (AML) when highly expressed; however, the mechanisms involved are unknown. We sought to model the effects of high MN1 expression in AML models to explore the underlying mechanisms.

Methodology/principal findings

We used cell lines and a genetically defined mouse model of AML to examine the effects of MN1 overexpression on prognosis and response to cytarabine and doxorubicin in vitro and in vivo. Murine AML that was engineered to overexpress MN1 became more aggressive in vivo, leading to shortened survival in both treated and control groups. In vitro murine AML cells that overexpressed MN1 became resistant to treatment with cytarabine and highly resistant to doxo

SUBMITTER: Pardee TS 

PROVIDER: S-EPMC3419213 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature