Upregulation of the Developmental Regulator, SALL1, in Human Leukemias
L Shatat, S Kiefer, L Robbins, Q Xie, M Rauchman, L Grosso, H Salman. Creighton University, Omaha, NE; St Louis University, St Louis, MO
Background: SALL1, a human homologue to Drosophila spalt, is a zinc finger transcription factor that regulates normal development. In humans, SALL1 is located on chromosome 16q12.1, encodes a protein of 1324 amino acids, and interacts with a nucleosome remodeling complex. Mutations in human SALL1 cause the autosomal dominant disorder, Townes-Brocks syndrome (TBS). In our lab, we have created a mouse model of TBS syndrome that phenocopies the human syndrome and expresses a truncated SALL1 protein. In addition to the TBS limb, ear, anal, and kidney defects, we observed that these mice also display severe myelodysplastic syndrome/ acute myeloid leukemia (AML).
Design: Immunohistochemistry studies were performed on AML (n=60) and non-neoplastic control bone marrow (n=10) paraffin tissue sections utilizing a monoclonal antibody directed against the N-terminal region of SALL1. Bone marrow samples from each group (AML, n=3; control, n=3) were tested by quantitative real time PCR using SALL1-specific primers to determine if SALL1 mRNA expression was affected in AML patients.
Results: We demonstrated that SALL1 was upregulated in 44/60 AML patients and not in normal controls. Consistent with its role as a transcription factor, SALL1 histochemical staining was nuclear.
These findings were confirmed by quantitative real time PCR where SALL1 mRNA was undetectable in all control samples and significantly upregulated in AML patients.
Conclusions: Data in mice and humans has linked the overexpression of SALL1 to AML neoplasias. Since the nucleosome remodeling complex that associates with SALL1 has been shown to regulate tumorogenesis in other cancers, it is tempting to speculate that the upregulation of SALL1 is functionally significant for the molecular pathogenesis of AML.
Wednesday, March 11, 2009 1:00 PM
Poster Session VI # 180, Wednesday Afternoon