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A molecular systems analysis of HOX PPI networks in hematopoiesis and leukemogenesis

Hox proteins are important regulators in hematopoiesis and their dysregulation by other factors results in different phenotypes during leukemia. To determine the interaction of other developmental proteins with Hox proteins implicated to have specific roles in hematopoiesis (HOXA7, HOXA9, HOXA10, HOXB3, HOXB4 and HOXC8), Cytoscape was used to create a protein-protein interaction network utilizing information in publicly available databases and literature. Hox genes regulate other genes but in turn can be dysregulated by specific fusion protein partners. HOXB3 provides the most significant complexes, indicating the importance of TALE proteins and of the MLL PHD finger in hematopoietic regulation. The ID3 complex, NUP98, MLL, and Notch1 are also key proteins for leukemia prevention and treatment.