Project description:mRNA profiles of leukemic B cells from 8-week-old leukemic (Eu-TCL1 and Eu-TCL1-Rab27DKO) mice were generated by 3'-sequencing, in triplicate.
Project description:Tcl1 tg mice develop a chronic lymphocytic leukemia (CLL) -like disease. To investigate the contribution of the adhesion molecule CD44 to CLL pathophysiology, we developed a CD19Cre CD44flox/flox Tcl1 tg mouse with a B cell specific CD44 deficiency (CD44ΔB Tcl1 tg). We used the Clariom S mouse microarray from Affymetrix to investigate transcriptional differeneces between Tcl1 tg and CD44ΔB Tcl1 tg mice
Project description:The function of ID4 in CLL development was studied in vivo using TCL1 transgenic mouse model that develop leukemia similar to human CLL. TCL1 mice with ID4 single knockout gene have accelerated CLL progression. Results from the animal study suggest ID4 as a tumor suppressor gene that might regulate cell proliferation and apoptosis in B lymphocytes. Gene expression in CD19-positive splenic B cells collected from 1-month old ID4+/-TCL1-tg and ID4+/+TCL1-tg mice was compared by microarray, the goal is to find ID4-regulated genes involved in CLL development.
Project description:To analyze expression differences between Trp53 pro-and deficient as well as Atm pro- and deficient murine CLL tumors developing in the Eµ-TCL1 mouse model, we analyzed splenocytes isolated from heavily infiltrated spleens of sick mice. To investigate differences in the response to cyclophosphamide, we also analyzed splenocytes from leukemic animals that were isolated twelve hours after intraperitoneal injection of cyclophosphamide.
Project description:Comparison of Chronic Lymphocytic Leukemia patients expressing high or low levels of ZAP70 mRNA: prognostic factors and interaction with the microenvironment. Zeta-associated protein 70 (ZAP70) is a widely recognized prognostic factor in chronic lymphocytic leukemia (CLL), but mechanisms by which its higher expression leads to a poor outcome remain to be fully explained. In an attempt to unveil unfavorable cellular properties linked to high ZAP70 expression, we used gene expression profiling to identify genes associated with disparities in B-cells from CLL patients expressing high versus low ZAP70 mRNA, measured by quantitative real-time PCR. Keywords: comparison of poor and good prognosis CLL patient transcriptome regarding ZAP70 expression
Project description:Immune deficiency is common in cancer, but the biological basis for this and ways to reverse it remains elusive. Here we present a mouse model of B cell chronic lymphocytic leukemia (CLL) that recapitulates changes in the non-malignant circulating T cells seen in patients with this illness.1 To validate this model, we examined changes in T cell gene expression, protein expression and function in Em-TCL1 transgenic mice as they developed CLL 2,3 and demonstrate that development of CLL in these transgenic mice is associated with changes in impaired T cell function and in gene expression in CD4 and CD8 T cells similar to those observed in patients with this disease. Infusion of CLL cells into non-leukemia bearing Em-TCL1 mice rapidly induces these changes, demonstrating a causal relationship between leukemia and the induction of T cell changes. This model allows dissection of the molecular changes induced in CD4 and CD8 T cells by interaction with leukemia cells and further supports the concept that cancer results in complex abnormalities in the immune microenvironment. Gene expression profiling was performed to determine whether Em-TCL1 murine model of chronic lymphocytic leukemia (CLL) mimics T cell defects induced by CLL cells in patients with CLL. Keywords: comparative gene expression profiling analysis.
Project description:The function of ID4 in CLL development was studied in vivo using TCL1 transgenic mouse model that develop leukemia similar to human CLL. TCL1 mice with ID4 single knockout gene have accelerated CLL progression. Results from the animal study suggest ID4 as a tumor suppressor gene that might regulate cell proliferation and apoptosis in B lymphocytes.
Project description:Comparison of Chronic Lymphocytic Leukemia patients expressing high or low levels of ZAP70 mRNA: prognostic factors and interaction with the microenvironment. Zeta-associated protein 70 (ZAP70) is a widely recognized prognostic factor in chronic lymphocytic leukemia (CLL), but mechanisms by which its higher expression leads to a poor outcome remain to be fully explained. In an attempt to unveil unfavorable cellular properties linked to high ZAP70 expression, we used gene expression profiling to identify genes associated with disparities in B-cells from CLL patients expressing high versus low ZAP70 mRNA, measured by quantitative real-time PCR. Experiment Overall Design: Two groups of seven CLL patients were compared, selected on the basis of either high or low ZAP70 mRNA expression. Total RNA from CD19+ purified cells was exctracted and hybidyzed on Affymetrix GeneChipî Human Genome U133 Plus 2.0 Array. Amplification, hybridization and scanning were done according to standard Affymetrix protocols (www.affymetrix.com). CEL files were ,normalized with RMA method.
Project description:Immune deficiency is common in cancer, but the biological basis for this and ways to reverse it remains elusive. Here we present a mouse model of B cell chronic lymphocytic leukemia (CLL) that recapitulates changes in the non-malignant circulating T cells seen in patients with this illness.1 To validate this model, we examined changes in T cell gene expression, protein expression and function in Em-TCL1 transgenic mice as they developed CLL 2,3 and demonstrate that development of CLL in these transgenic mice is associated with changes in impaired T cell function and in gene expression in CD4 and CD8 T cells similar to those observed in patients with this disease. Infusion of CLL cells into non-leukemia bearing Em-TCL1 mice rapidly induces these changes, demonstrating a causal relationship between leukemia and the induction of T cell changes. This model allows dissection of the molecular changes induced in CD4 and CD8 T cells by interaction with leukemia cells and further supports the concept that cancer results in complex abnormalities in the immune microenvironment. Gene expression profiling was performed to determine whether Em-TCL1 murine model of chronic lymphocytic leukemia (CLL) mimics T cell defects induced by CLL cells in patients with CLL. Experiment Overall Design: CD4 T cells and CD8 T cells were obtained from spleens of B6C3 and Em-TCL1 transgenic murine model of CLL or from peripheral blood mononuclear cells of previously untreated patients with CLL and healthy individuals (Pubmed ID: 15965501). Gene expression profiling was performed using total RNA and the data were analysed to compare gene expression profile of CLL to healthy within or between the species.