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BMI1 oncogene is a catalytic member of epigenetic repressor polycomb group proteins. It plays a critical role in the regulation of gene expression pattern and consequently several cellular processes during development, including cell cycle progression, senescence, aging, apoptosis, angiogenesis, and importantly self-renewal of adult stem cells of several lineages. Preponderance of evidences indicates that deregulated expression of PcG protein BMI1 is associated with several human malignancies, cancer stem cell maintenance, and propagation. Importantly, overexpression of BMI1 correlates with therapy failure in cancer patients and tumor relapse. This review discusses the diverse mode of BMI1 regulation at transcriptional, posttranscriptional, and posttranslational levels as well as at various critical signaling pathways regulated by BMI1 activity. Furthermore, this review highlights the role of BMI1 as a biomarker and therapeutic target for several subtypes of hematologic malignancies and the importance to target this biomarker for therapeutic applications.
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