However, high-level HOX gene expression alone in AML is not sufficient to result in IRX3 expression, because only 40% of HOXA9+ cases express IRX3. This suggests that additional factors act combinatorially to induce IRX3. For example, the Wnt signaling pathway, which is active in AML, induces IRX3 in forebrain development (Braun et al., 2003). This evidence concerns the gene IRX3 and acute myeloid leukemia.