Overexpression of BMI1 confers clonal cells resistance to apoptosis and contributes to adverse prognosis in myelodysplastic syndrome

The polycomb group (PcG) protein BMI1 plays a critical role in regulating self renewal capacity of both normal and leukemic stem cells. BMI1 is frequently overexpressed in several types of cancer, which is associated with poor prognosis. However, there are few researches on BMI1 in myelodysplastic syndromes (MDS). In this study, we reported that overexpression of BMI1 protein was detected in MDS patients, and inversely correlated with the apoptosis of CD34+ cells. In vitro overexpression of BMI1 facilitated proliferation and inhibited apoptosis of MDS-L cells. The overexpression of BMI1 could downregulate apoptosis sensitivity to cytotoxic agents in MDS-L cells; on the contrary, MDS-L cells could be rendered apoptosis-sensitive by BMI1 knockdown. Overexpression of BMI1 antagonised apoptosis by downregulating several apoptosis-related proteins, such as p16(INK4a), phospho-p53 (Ser46) and caspase 3/9. In addition, overexpression of BMI1 was correlated with an elevated IPSS score and a shorter survival. Collectively, overexpression of BMI1 induces resistance to apoptosis and contributes to adverse prognosis in MDS. BMI1 could serve as a therapeutic target for patients with MDS. (C) 2011 Elsevier Ireland Ltd. All rights reserved.