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

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. 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. 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.