Project description:This study demonstrated that genetic background is critical to the STAT5B-mediated lymphomagenesis probably through regulation of STAT5B activation, which results in the alteration of many tumorigenic genes. Chemopreventive compounds that can reduce STAT5B phosphorylation and/or the STAT5B signaling pathway can efficiently block lymphomagenesis, demonstrating that the NOD.Stat5bTg mouse is an excellent model for testing novel chemopreventive strategies.
Project description:A series of dual-channel gene expression profiles obtained using Rosetta/Merck Mouse TOE 75k microarrays was used to examine the sex-dependent and STAT5b-dependent differences in gene expression in adult mouse liver. This series is comprised of 4 pools of 3 randomly chosen independent wildtype male and female mouse liver cDNA samples and 4 pools of 3 randomly chosen independent STAT5b-deficient male and female mouse liver cDNA samples, totaling 16 pools. The pools were paired randomly to generate 4 comparisons of M-WT:F-WT, M-WT:M-KO, F-KO:F-WT, and F-KO:M-KO. Comparison of the set of sex-dependent genes with the set of genes responsive to the loss of STAT5b in males shows that 75% of the sex-specific genes were also regulated by STAT5b in males. Only 20% of the sex-specific genes retained sex-specificity in the absence of STAT5b, indicating a large role for STAT5b in sex-specific liver gene expression. Keywords: genetic knockout and sex response
Project description:To explore transcriptional similarities between human and murine Anaplastic Large Cell Lymphoma (ALCL) cell lines, RNA sequencing was performed across both species. The human cell lines included SU-DHL-1, DEL, SUP-M2, Karpas-299, SR-786, Mac1 and Mac2a. Additionally, murine cell lines derived from tumors with distinct genetic backgrounds (NPM-ALK(Tg/+), NPM-ALK(Tg/+)Cdk6-/- and NPM-ALK(Tg/+)Stat5b-/-) were analyzed to identify gene expression differences associated with tumor development in the absence of CDK6 or STAT5B.
Project description:T-Large Granular Lymphocyte Leukemia is a rare lymphoproliferative disorder characterized by the abnormal clonal expansion of cytotoxic T-LGL. The immunophenotype, clinical presentation, and prognosis are associated with activating mutations in STAT3 and STAT5B genes, which define four distinct subsets of the disease: CD8+ with STAT3 mutation, CD8+ wild-type, CD4+ with STAT5B mutation, and CD4+ wild-type. RNA-seq data analysis of these patients reveals aberrant genes and non-coding RNA expression, pathways dysregulation, and the peculiarities of STAT3 mutated cases, which are associated with severe symptoms. This study offers new insights into the pathogenesis and clinical characteristics of T-LGLL patients, highlighting potential new targetable oncogenic axes for this disease.
Project description:This study demonstrated that genetic background is critical to the STAT5B-mediated lymphomagenesis probably through regulation of STAT5B activation, which results in the alteration of many tumorigenic genes. Chemopreventive compounds that can reduce STAT5B phosphorylation and/or the STAT5B signaling pathway can efficiently block lymphomagenesis, demonstrating that the NOD.Stat5bTg mouse is an excellent model for testing novel chemopreventive strategies. To elucidate the molecular mechanism underlying the activation of Stat5b upon lymphoma onset, we profiled gene expression in thymocytes of NOD.Stat5b mice, Gene expression was analyzed with the Illumina's MouseRef-8 v2.0 Expression beadchips
Project description:Here we report both TET1-WT and catalytically dead mutant TET1 (TET1-MUT) directly interact with STAT5B in PDX2 B-ALL cells. To study the landscape of TET1 and STAT5B binding in whole genomic DNA and test if the STAT5B binding signal is affected by TET1, we conduct the ChIP-seq assay with flag antibody (TET1-WT, TET1-MUT) and STAT5B antibody (sgNS or sgTET1) respectively. The results showed that TET1 bound peaks overlap with STAT5B very well and the tag density of STAT5B on target genes decreases in TET1-impeded cells. We conclude that TET1 recruit STAT5B to the promoters of its target genes and further promote the target genes’ transcriptions.
Project description:Stat5b gene is located at IDD4 type 1 diabetes susceptibility interval, and is mutated in NOD mice. This mutation has been linked to diabetes with strong association with autoimmune aetiology. We have treated MIN6 pancreatic beta cell line with Stat5b siRNA and analyzed the differential expression profile in control siRNA treated versus Stat5b siRNA treated cells in an effort to understand the role of Stat5b in diabetes.