SALL4 as a transcriptional and epigenetic regulator in normal and leukemic hematopoiesis

Abstract

Abstract In recent years, there has been substantial progress in our knowledge of the molecular pathways by which stem cell factor SALL4 regulates the embryonic stem cell (ESC) properties, developmental events, and human cancers. This review summarizes recent advances in the biology of SALL4 with a focus on its regulatory functions in normal and leukemic hematopoiesis. In the normal hematopoietic system, expression of SALL4 is mainly enriched in the bone marrow hematopoietic stem/progenitor cells (HSCs/HPCs), but is rapidly silenced following lineage differentiation. In hematopoietic malignancies, however, SALL4 expression is abnormally re-activated and linked with deteriorated disease status in patients. Further, SALL4 activation participates in the pathogenesis of tumor initiation and disease progression. Thus, a better understanding of SALL4’s biologic functions and mechanisms will facilitate development of advanced targeted anti-leukemia approaches in future.

Keywords

• Pluripotency
• Hematopoietic stem and progenitor cells
• Apoptosis
• Transgenic
• Wnt/β-catenin signaling
• Mixed-lineage leukemia