Figure 6.

Schematic model depicting Hoxa-dependent myeloid transformation by MLL oncoproteins. Differentiation-inducing signals from the bone marrow microenvironment promote commitment of normal pluripotential HSCs toward terminal myeloid development that is associated with the loss of 5′Hoxa gene expression. MLL oncoproteins disrupt this critical regulatory circuit, enhancing myeloid progenitor self-renewal via maintenance of 5′Hoxa gene expression, blocking differentiation events ultimately progressing to AML.