The next new target in leukemia: The embryonic stem cell gene .

The embryonic stem (ES) cell gene has recently been identified as a new target for cancer therapy, including leukemia. SALL4 is expressed in ES cells and during embryonic development, but is absent in most adult tissues. It is, however, aberrantly expressed in various solid tumors and hematologic malignancies such as myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Aberrant expression of SALL4 is frequently associated with a more aggressive cancer phenotype, which includes high-risk MDS and its progression to AML. SALL4 contributes to leukemogenesis through multiple pathways including the repression of PTEN and the activation of HOXA9 expression. Targeting the SALL4/PTEN pathway by blocking the protein-protein interaction of SALL4 and its associated epigenetic complex, nucleosome remodeling and deacetylase complex (NuRD), might be a novel approach to treating AML and holds great potential for the treatment of other SALL4-mediated oncogenic processes such as high-risk MDS and solid tumors.