Bmi-1 over-expression plays a secondary role in chronic myeloid leukemia transformation.
It has been demonstrated that over-expression of Bmi-1 occurs in a variety of cancers, including several types of leukemia. This gene plays a key role in the self-renewal of stem cells. Leukemic cells lacking Bmi-1 underwent proliferation arrest and showed signs of differentiation and apoptosis. These findings led to the proposal of Bmi-1 as a potential target for therapeutic intervention in cancer. In this study, we investigated the role of Bmi-1 in chronic myeloid leukemia (CML). Using qRT-PCR, we demonstrated a significantly increased level of Bmi-1 transcript in CML cells. Using array analysis, we determined the deregulation of several genes after Bmi-1 silencing. Proapoptotic genes BAD and TRADD, and CASP8, p16-INK4, BRCA2, Notch4 and Wnt-8B were elevated. PLK1, SOD1, E2F-3, two retinoblastoma binding proteins (RBQ1 and RBBP4) and HDGF were reduced after Bmi-1 inhibition. Additionally, we tested the impact of Bmi-1 siRNA on CML cell growth; however, there was no apparent change after Bmi-1 suppression. Despite the fact that Bmi-1 deregulation occurs in CML and its expression is connected to several oncogenic processes, Bmi-1 seems to play a secondary role in CML transformation.
Merkerova
Michaela
M
Institute of Hematology and Blood Transfusion, Department of Molecular Genetics, Prague, Unemocnice 1, 128 20 Prague 2, Czech Republic. michaela.merkerova@uhkt.cz
Bruchova
Hana
H
Kracmarova
Alzbeta
A
Klamova
Hana
H
Brdicka
Radim
R
D000328:Adult; D049109:Cell Proliferation; D005260:Female; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic; D020868:Gene Silencing; D006801:Humans; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000096:biosynthesis*; D063150:Polycomb Repressive Complex 1; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D034741:RNA, Small Interfering / Q000378:metabolism; D012097:Repressor Proteins / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction
C069077:BMI1 protein, human; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D012097:Repressor Proteins; D063150:Polycomb Repressive Complex 1