title: Overexpression of BMI1 confers clonal cells resistance to apoptosis and contributes to adverse prognosis in myelodysplastic syndrome.
abstract: 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.
authors: Department of Hematology, The Sixth People's Hospital Affiliated to Shanghai Jiaotong University, China.
authors: Feng
authors: F
authors: Xu
authors: Rui
authors: R
authors: Yang
authors: Lingyun
authors: L
authors: Wu
authors: Qi
authors: Q
authors: He
authors: Zheng
authors: Z
authors: Zhang
authors: Qingxia
authors: Q
authors: Zhang
authors: Yujuan
authors: Y
authors: Yang
authors: Juan
authors: J
authors: Guo
authors: Chunkang
authors: C
authors: Chang
authors: Xiao
authors: X
authors: Li
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D018952:Antigens, CD34 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D059447:Cell Cycle Checkpoints; D002460:Cell Line; D049109:Cell Proliferation; D002999:Clone Cells; D005260:Female; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D063150:Polycomb Repressive Complex 1; D011379:Prognosis; D016016:Proportional Hazards Models; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D015996:Survival Rate; D013997:Time Factors; D014162:Transfection; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D018952:Antigens, CD34; D051017:Apoptosis Regulatory Proteins; C069077:BMI1 protein, human; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D063150:Polycomb Repressive Complex 1