Project description:The adult T-cell leukemia/lymphoma cell line KK1 with low RhoH expression was stably transfected with either an empty expression vector or this same vector expressing human RhoH. The transcriptomes of these two daughter lines were then compared by differential microarray analysis
Project description:We exploited the use of I-BET762, copanlisib, and bardoxolone methyl inhibitors as triple combination to understand the interactions between these three pathways in Adult T cell leukemia/lymphoma.
Project description:Abstract: Adult T-cell leukemia/lymphoma (ATL) is an aggressive and fatal disease. We have examined 18 ATL patient samples using Affymetrix HG-U133A2.0 arrays. Using the BRB array program, we identified genes differentially expressed in leukemia cells compared to normal lymphocytes. Several unique genes were identified that were overexpressed in leukemia cells including TNFSF11, RGS13, MAFb, CSPG2, C/EBPalpha and TCF4. 200 of the most highly overexpressed ATL genes were analyzed by the PathwayStudio 4.0 program. ATL leukemia cells were characterized by an increase in genes linked to "central" genes CDC2/cyclin B1, SYK/LYN, PCNA and BIRC5. Because of its potential therapeutic importance, we focused our studies on the regulation and function of BIRC5, whose expression was increased in 13 of 14 leukemia samples. TCF4 reporter assays and transfection of DN-TCF4 demonstrated that TCF4 regulates BIRC5 gene expression. Functionally, transfection of ATL cells wi BIRC5 shRNA decreased BIRC5 exprression and cell viability 80%. Clinical treatment of ATL patients with Zenapax or bortezomib decreased BIRC5 expression and cell viability. These experiments represent the first direct experimental evidence that BIRC5 plays an important role in ATL cell viability and provides important insight into ATL genesis and potential targeted therapies. Experiment Overall Design: Gene expression profiles of 7 control and 18 ATL patient samples were analyzed using Affymetrix HG-U133A2.0 arrays.
Project description:We established HTLV-1/EBV co-infected cell lines from Adult T-cell Leukemia/Lymphoma (ATLL) patients, and found that they are derived from germinal center (GC) B-cells or transitional B-cells between GC-B-cells and memory B-cells by using gene expression profiling (GEP) analysis. Expression of CD25 and TSLC1, which are diagnostic markers of ATLL cells, were identified in the ATLL-derived B-cell lines as discriminators of EBV-imortalized cell lines, indicating that HTLV-1 infection leads to express CD25 and TSLC1.
Project description:This phase II trial studies how well giving lenalidomide with or without rituximab works in treating patients with progressive or relapsed chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), prolymphocytic leukemia (PLL), or non-Hodgkin lymphoma (NHL). Biological therapies, such as lenalidomide, may stimulate the immune system in different ways and stop cancer cells from growing. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving lenalidomide together with or without rituximab may kill more cancer cells.
Project description:This study is an integrated molecular study of adult T-cell leukemia/lymphoma which includes whole-exome (n = 81), whole-genome (n = 48), and transcriptome sequencing data (n = 57) as well as methylation (n = 109) and SNP array data (n = 426)
Project description:Adult T-cell leukemia/lymphoma (ATL) is a highly aggressive hematological malignancy derived from mature CD4+ T-lymphocytes. In this study, we performed RNA-sequencing (RNA-seq) analysis for ATL samples including 9 primary tumors and 1 ATL cell line to clarify gene expression profiles in this disease.
Project description:Adult T-cell leukemia-lymphoma (ATLL) is an HTLV-1-associated lymphoproliferative malignancy that is frequently fatal. We compared gene expression profiles (GEPs) of leukemic specimens from 9 patients with ATLL at the time of diagnosis and immediately after combination therapy with zidovudine (AZT) and interferon alpha (IFN). GEPs were also related to genetic aberrations determined by comparative genomic hybridization. We identified several genes anomalously over-expressed in the ATLL leukemic cells at the mRNA level, including LYN, CSPG2 and LMO2, with confirmation of LMO2 expression confirmed in ATLL cells at the protein level. In vivo AZT- and IFNa treatment evoked a marked induction of interferon-induced genes accompanied by repression of cell-cycles regulated genes including those encoding ribosomal proteins. Remarkably, patients not responding to IFNa/AZT differed most from responding patients in relative over expression of these same IFN-responsive genes, as well as components of the antigen processing and presentation apparatus. Demonstration of specific gene expression signatures associated with response to AZT-IFNa therapy may provide novel insights into the mechanisms of action in ATLL. compound_treatment_design