Expression data of chronic lymphocytic leukemia patient samples from the REACH study
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE58211 | GEO | 2014/07/30
SECONDARY ACCESSION(S): PRJNA251740
REPOSITORIES: GEO
Similar Datasets
Project description:We assessed genome-wide expression of available pretreatment specimens from CLL patients enrolled in REACH, a study of fludarabine and cyclophosphamide FC or R-FC (addition of rituximab to FC) in relapsed CLL, to understand the disease heterogeneity and explore genes that may be prognostic or predictive of benefit from R-FC treatment. REACH (NCT00090051) was registered at www.clinicaltrials.gov. This dataset supports the manuscript "PTK2 expression and immunochemotherapy outcome in chronic lymphocytic leukemia" by Weisser et al. 300 available pretreatment specimens from patients enrolled in REACH trial were analyzed. Additional contributers: REACH study investigators and patients
2014-07-30 | E-GEOD-58211 | biostudies-arrayexpress
Project description:Longitudinally sampled peripheral blood samples of 9 CLL patients were subjected to single cell RNA sequencing before and at relapse after chemotherapy with fludarabine, cyclophosphamide and rituximab (FCR); allogeneic hematopoietic stem cell transplantation (RIC allo-HSCT); ibrutinib treatment, or before and after transformation to Richter's syndrome.
2021-06-09 | GSE165087 | GEO
Project description:Purpose: Accurate prediction of clinical response is the prerequisite for individualized therapy in chronic lymphocytic leukemia (CLL). We hypothesized that sequential assessment of gene expression changes early during therapy may well reflect behaviour of the leukemic clone in response to specific drugs. Patients and Methods: Gene expression profiles (GEP) were determined in CD19+ selected B-cells from 20 patients treated with fludarabine and cyclophosphamide (FC) (N=10) or FC plus rituximab (FCR) (N=10). Samples were collected in the first cycle before and within 48hours after initiation of treatment. GEP analysis was stratified by clinical response 3 months after start of therapy. Results: GEP before treatment detected high expression of 34 genes correlated with response and 32 genes correlated with resistance to therapy. These genes were related to regulation of apoptosis, cell cycle, cell adhesion, and signal transduction. Different results were obtained with sequential GEP: Sixteen genes were up-regulated after rituximab infusion in non-responders. Rituximab therapy resulted in down-regulation of AKT1 indicating involvement of the PI3-kinase pathway in CD20-signaling. Up-regulation of 24 genes after FC (including ITPKB (inositol 1,4,5-trisphosphate 3-kinase) and CD44) and of 36 genes after FCR (including CD49d) was associated with resistance. Down-regulation of CTLA4 correlated with poor response to FC. CD44, CD49d and the PI3-kinase signaling pathway were confirmed as potential therapeutic targets to overcome resistance by (protein analysis) or functional experiments. Conclusion Sequential GEP provides rapid and relevant information for prediction of response and resistance. This approach could be used to guide and adapt individualized therapy in CLL. 50 Samples from CD19 selected B-cells, three treatments (rituximab, FC and RFC), 10 replicates for each treatment, 20 replicates for control condition
2011-03-01 | E-GEOD-15490 | biostudies-arrayexpress
Project description:Mitochondrial mutations have the potential to act as natural barcodes that allow the tracking of heterogenous cell populations at the single cell level, but thus far, the dynamics of mitochondrial mutations across time and tissue compartments have not been extensively studied. This dataset was generated using mtscATAC-seq to track mitochondrial mutations in peripheral blood, bone marrow and lymph node from 9 patients with chronic lymphocytic leukemia (CLL) across different clinical scenarios. Our in-depth analysis reveals different patterns of dynamisms in mitochondrial mutations in patients undergoing watchful waiting, chemotherapy with fludarabine, cyclophosphamide and rituximab (FCR), allogeneic stem cell transplantation, ibrutinib treatment or transformation to Richter’s syndrome. We provide evidence that mitochondrial mutations can link CLL subclones with distinct chromatin cell states. Mitochondrial mutations appear to recapitulate disease history in CLL, providing patient-level support of the concept of in vivo natural barcodes as a means for understanding clonal dynamics in cancer.
2021-06-09 | GSE163579 | GEO
Project description:Purpose: Accurate prediction of clinical response is the prerequisite for individualized therapy in chronic lymphocytic leukemia (CLL). We hypothesized that sequential assessment of gene expression changes early during therapy may well reflect behaviour of the leukemic clone in response to specific drugs. Patients and Methods: Gene expression profiles (GEP) were determined in CD19+ selected B-cells from 20 patients treated with fludarabine and cyclophosphamide (FC) (N=10) or FC plus rituximab (FCR) (N=10). Samples were collected in the first cycle before and within 48hours after initiation of treatment. GEP analysis was stratified by clinical response 3 months after start of therapy. Results: GEP before treatment detected high expression of 34 genes correlated with response and 32 genes correlated with resistance to therapy. These genes were related to regulation of apoptosis, cell cycle, cell adhesion, and signal transduction. Different results were obtained with sequential GEP: Sixteen genes were up-regulated after rituximab infusion in non-responders. Rituximab therapy resulted in down-regulation of AKT1 indicating involvement of the PI3-kinase pathway in CD20-signaling. Up-regulation of 24 genes after FC (including ITPKB (inositol 1,4,5-trisphosphate 3-kinase) and CD44) and of 36 genes after FCR (including CD49d) was associated with resistance. Down-regulation of CTLA4 correlated with poor response to FC. CD44, CD49d and the PI3-kinase signaling pathway were confirmed as potential therapeutic targets to overcome resistance by (protein analysis) or functional experiments. Conclusion Sequential GEP provides rapid and relevant information for prediction of response and resistance. This approach could be used to guide and adapt individualized therapy in CLL.
2011-03-01 | GSE15490 | GEO
Project description:Characterization of the transcriptional changes occurring at the single-cell level during the progression of a chronic lymphoid leukaemia treated with Rituximab, Fludarabine and Cyclophosphamide.
2020-10-27 | GSE150930 | GEO
Project description:Although in 80% of CLL cases that require therapy is possible to achieve a complete remission using a combination of fludarabine, anti-CD20 in conjunction with cyclophosphamide and/or mitoxantrone, 20% of patients do not achieve disease control with this conventional approach. The main reason of complete remission failure is chemorefractoriness to fludarabine that occurs in up to 10% of patients requiring treatment. In order to identify new molecular predictors of refractoriness as well as druggable therapeutic targets, we combined next-generation sequencing and copy number analyses. Affymetrix SNP array analysis was performed according to the manufacturer's directions on DNA extracted from cryopreserved diagnostic samples.
2014-04-30 | GSE51711 | GEO
Project description:Purpose:To identify resistance mechanisms for the chemotherapeutic drug fludarabine in chronic lymphocytic leukemia (CLL), as innate and acquired resistance to fludarabine-based chemotherapy represents a major challenge for long-term disease control. Methods: We employed piggyBac transposon-mediated mutagenesis, combined with next-generation sequencing, to identify genes that confer resistance to fludarabine in a human CLL cell line. Results: RNA-seq profiling of fludarabine-resistant cells suggested deregulated MAPK signaling as involved in mediating drug resistance in CLL.
2016-03-31 | GSE75844 | GEO
Project description:Although in 80% of CLL cases that require therapy is possible to achieve a complete remission using a combination of fludarabine, anti-CD20 in conjunction with cyclophosphamide and/or mitoxantrone, 20% of patients do not achieve disease control with this conventional approach. The main reason of complete remission failure is chemorefractoriness to fludarabine that occurs in up to 10% of patients requiring treatment. In order to identify new molecular predictors of refractoriness as well as druggable therapeutic targets, we combined next-generation sequencing and copy number analyses. Affymetrix SNP array analysis was performed according to the manufacturer's directions on DNA extracted from cryopreserved diagnostic samples. Copy number analysis of Affymetrix SNP 6.0 arrays was performed for 10 FR-CLL samples and their paired normal (non-tumoral) DNA samples, processed in the same experiment and deposited (discovery set). The analysis was then extended to 29 additional FR-CLL tumoral samples and 3 Normal DNAs processed in the same experiment, including the Reference Normal DNA provided by Affymetrix (screening set).
2014-04-30 | E-GEOD-51711 | biostudies-arrayexpress
Project description:Chronic lymphocytic leukemia (CLL) is a heterogeneous malignancy, characterized by a variable clinical course. While clinical and laboratory parameters are increasingly being used to refine prognosis, they do not accurately predict response to commonly used therapy. We used gene expression profiling to generate and further refine prognostic and predictive markers. Genomic signatures that reflect progressive disease and responses to chemotherapy or chemo-immunotherapy were created using cancer cell lines and patient leukemia samples. We validated these signatures using independent clinical data from four separate cohorts representing a total of 301 CLL patients. A prognostic genomic signature created from patient leukemic cell gene expression data coupled with clinical parameters could statistically differentiate patients with stable or progressive disease in the training dataset. The progression signature was then validated in two independent datasets, demonstrating a capacity to accurately identify patients at risk for progressive disease. In addition, two distinct genomic signatures that predict response to chlorambucil or pentostatin, cyclophosphamide, and rituximab were also generated and were shown to accurately distinguish responding and non-responding CLL patients. Microarray analysis of CLL patientsâ lymphocytes can be used to refine prognosis and predict response to different therapies. These results have direct implications for standard and investigational therapeutics in CLL patients. Experiment Overall Design: For the predictive genomic signature or response to pentostatin, cyclophosphamide, and rituximab, 20 CLL leukemia samples were used in the training set, and 20 CLL leukemia samples were used in the validation set
2009-11-11 | E-GEOD-10137 | biostudies-arrayexpress