TARGETING OF SALL4 FOR THE TREATMENT AND DIAGNOSIS OF PROLIFERATIVE DISORDERS ASSOCIATED WITH MYELODYSPLASTIC SYNDROME (MDS)

摘要

The present invention discloses nucleic acids, proteins, and antibodies forSALL4 (including isoforms SALL4A, SALL4B, and SALL4C), a zinc finger transcriptionalfactor. Further, methods are disclosed which demonstrate that constitutiveexpression of SALL4 increases leukemogenic potential in cells of model animalsystems. Moreover, constitutive expression of select isoforms (e.g., SALL4B)in transgenic mice demonstrate that these animals develop myelodysplasticsyndrome (MDS)-like signs and symptoms, including subsequent acute myeloidleukemia (AML), which is transplantable. The disclosure also provides methodsfor identifying and purifying embryonic stem cells, adult stem cells, cancerstem cells, including leukemia stem cells, methods for identifying substanceswhich bind to and/or modulate SALL4, methods for diagnosing MDS in a subject,and methods of treating a subject presenting MDS, AML and other forms of leukemia.