The Molecular Signature Induced by HMGA1 During Lymphoid Tumorigenesis. Mus musculus

We are exploring the molecular pathways activated during lymphoid transformation with the long term goal of developing better therapies. Our focus is the HMGA1a oncogene because our studies indicate that it plays an important role in aggressive human lymphoid leukemia and lymphoma. We have developed the transgenic mouse over-expressing HMGA1a in lymphoid cells that develop aggressive lymphoid tumors by 8-10 months with histopathologic findings resembling human T-cell acute lymphocytic leukemia. By analyzing the gene expression profiles of our HMGA1a mouse model we plan to identify molecular pathways activated by HMGA1a in lymphoid transformation. Results from these studies will enhance our understanding of the pathogenesis of lymphoid malignancies and should lead to the development of better therapies. Overall design: A total of 20,669 genes represented on the Affymetrix Mouse 430 2.0 GeneChipTM array were screened with cRNA prepared from lymphoid cells of HMGA1a transgenic mice at different stages in tumorigenesis. These mice develop lymphoid tumors with complete penetrance at 8-12 months of age. We isolated RNA from splenocytes at 2 months (before tumors develop) and at 12 months (after tumors are well-established). These results were compared to splenocytes from control littermates. We used two statistical approaches to define differentially expressed genes, including a parametric (Partek genomics suite analysis) and nonparametric (CAM) approach.