342. RUNX1 Increases Proliferation of Embryoid Bodies Derived from Human Embryonic Stem Cells

Abstract

RUNX1 is an essential gene for mouse hematopoietic development. Mouse knockout models for RUNX1 or its binding partner, core binding factor |[beta]| (CBF|[beta]|), are embryonic lethal and lack definitive hematopoiesis. CBF|[beta]|-SMMHC (INV), encoded by the inv(16) chromosomal translocation in approximately 8% of acute myeloid leukemia (AML) cases, is a fusion protein comprising of CBF|[beta]| and the rod domain of smooth muscle myosin heavy chain (SMMHC). INV inhibits the expression of RUNX1-regulated genes, by sequestering RUNX1 and by directly repressing RUNX1- regulated genes. Recently, we reported that dominant inhibition of endogenous RUNX1 by lentivector-expressed INV inhibited proliferation of human and mouse myeloid progenitors. Conditional exogenous expression of RUNX1 using an estrogen receptor lentivector system in mouse primary HSPCs, resulted in increased proliferation [D'Costa, 2005]. Although RUNX1 is established as a key regulator of hematopoietic development in the mouse embryo, its role in human hematopoietic development has not been extensively studied for lack of an appropriate model. The availability of several human embryonic stem cell (HESC) lines provides a potential new system with demonstrated utility for the study of human embryonic hematopoiesis.