The Role of ASXL1/2 and Their Associated Proteins in Malignant Hematopoiesis

Purpose of the Review: Advances in genomic and epigenetic research have uncovered a central role for aberrant epigenetic regulation in the pathogenesis of myeloid malignancies. In the current review, we summarize the roles of ASXL1/2 and their associated proteins in normal and malignant hematopoiesis. Recent Findings: ASXL1/2 and their associated proteins, e.g., polycomb repressive complex 2 proteins, play key roles in regulating hematopoietic stem cell (HSC) functions. Genetic studies reveal that ASXL1/2 and their associated proteins play important roles for the establishment and maintenance of the cell fates of HSCs. Alterations of the genes coding ASXL1/2 and their associated proteins lead to the development of hematological malignancies. Summary: Epigenetic regulation is crucial for normal hematopoiesis. Alteration of multiple epigenetic modifiers contributes to myeloid malignancies. Understanding the molecular mechanisms is critical for further studying ASXL1/2 and their associated proteins in hematopoiesis and developing new therapeutic strategies to treat myeloid malignancies.