Bmi-1 over-expression plays a secondary role in chronic myeloid leukemia transformation

Abstract

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.

Keywords:

• Bmi-1
• CML
• expression arrays
• proliferation
• siRNA