Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA336365 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| Other | ||||
| SRR4462520_1.fastq.gz | Fastqsanger.gz | |||
| SRR4462520_2.fastq.gz | Fastqsanger.gz | |||
| SRR4462521_1.fastq.gz | Fastqsanger.gz | |||
| SRR4462521_2.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 15 |
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Project description:Single-cell DNA and RNA sequencing over a 29 year period of a CLL patient demonstrating evolution of multiple cell clones
| PRJNA336364 | ENA
Project description:<p>Chronic lymphocytic leukemia (CLL) is a frequent B-cell malignancy characterized by recurrent somatic chromosome alterations and a low level of point mutations. Here we present single nucleotide polymorphism (SNP) microarray analyses of a single CLL patient over 29-years of observation and treatment, and transcriptome and whole genome sequencing at selected timepoints. We identified chromosome alterations of 13q14-, 6q- and 12q+ in early cell clones, elimination of clonal populations following therapy, and subsequent appearance of a clone containing trisomy 12 and a chromosome 10 copy neutral loss of heterogeneity (LOH) that marks a major population dominant at death. Serial single cell RNA sequencing revealed elevated mRNA expression of the FOS, JUN and KLF4 genes just before the appearance of acute disease requiring therapy. This gene expression pattern became undetectable following therapy, but reoccurred following relapse. Transcriptome evolution indicates that complex expression changes occur over time. In conclusion, CLL can evolve gradually during indolent phases, and undergo rapid changes following therapy. </p>
| phs001181 | dbGaP
Project description:CD38 expression is an important prognostic marker in CLL with high levels of CD38 associated with shorter overall survival. In this study, we used gene expression profiling and protein analysis of highly purified cell-sorted CD38+ and CD38- chronic lymphocytic leukemia cells to elucidate a molecular basis for the association between CD38 expression and inferior clinical outcome. Paired CD38+ and CD38- CLL cells derived from the same patient were shown to be monoclonal by VH gene sequencing but despite this, CD38+ CLL cells possessed a distinct gene expression profile when compared with their CD38- sub-clones. Experiment Overall Design: These experiments compared the gene expression profile of CD38+ and CD38- sub-clones derived from 6 individual CLL patients.
2007-11-11 | E-GEOD-6321 | biostudies-arrayexpress
Project description:To investigate the longitudinal mutational patterns arising in Lynch Syndrome associated tumors we interrogated the genomes of five different cancers that arose over a period of 10 years in a patient who underwent resection in the absence of chemotherapy and radiation for each cancer. These included a papillary transitional cell carcinoma (PTCC) in the renal pelvis, a duodenal carcinoma, two separate CRCs that arose 3 years apart, and multiple regions of a triple negative breast cancer (TNBC). In each case we flow sorted tumor fractions from archived formalin fixed paraffin embedded (FFPE) tissue and profiled the tumor genomes with whole genome copy number variant (CNV) arrays and whole exome sequencing. These data were then used to identify the pathogenic variant underlying the diagnosis of LS, and to compare and contrast the CNV, mutational and neoepitope patterns across these divergent tumors that arose over a 10 year period. These results provide a unique analysis of distinct MSI+ tumors arising in a single LS patient.
2020-04-30 | GSE146670 | GEO
Project description:The identification of gene mutation and structural genomic aberrations that are critically involved in CLL pathogenesis is still evolving. One may postulate that genomic driver lesions with effects on CLL proliferation, apoptosis thresholds, or chemotherapy resistance should increase in frequency over time when measured sequentially in a large CLL cohort. We sequentially sampled a large, well-characterized CLL cohort at a mean of 4 years between samplings. The paired analysis included 156 patients, of whom 114 remained untreated and 42 received intercurrent therapies. Results: we identify a strong effect of intercurrent therapies on the frequency of acquisition of aCNAs in CLL. Importantly, the spectrum of acquired genomic changes was largely similar in patients that did or did not receive intercurrent therapies; therefore, various genomic changes that become part of the dominant clones are often already present in CLL cell populations prior to therapy. Further, we provide evidence that therapy of CLL with preexisting TP53 mutations results in the outgrowth of genomically very complex clones which dominate at relapse. Using complementary technologies directed at the detection of genomic events that are present in substantial proportions of of the clinically relevant CLL disease bulk, we capture aspects of genomic evolution in CLL over time, including increases in the frequency of genomic complexity, specific recurrent aCNAs, and TP53 mutations.
2013-04-19 | GSE45565 | GEO
Project description:NOX1 gene is member of the NADPH-dependent superoxide producing enzyme family. It generates reactive oxygen species (ROS) in regulated manner in response to growth factors, cytokines and calcium signal. Low levels of ROS play role in many processes including cell proliferation, inflammatory response and mitogenesis. NOX1 over-expression in colon cancer cell lines as well as surgical samples suggests a role in colon cancer. We identified unique target sequences of siRNAs for post-transcriptional silencing of NOX1. Gene specific and scrambled (control) sequence carrying U6 promoter/shRNA cassettes were cloned into GFP expression vector. Stable clones were selected based on NOX1 expression after transient transfection of HT-29 cells. Clone 6A and 6C showed 70-80% decrease in NOX1 expression. The cells were expanded and analyzed further. We measured decreased ROS production, cell proliferation and G1/S block of the cell cycle. HT-29 parental cells, clone SA (scrambled) and clone 6A (gene specific) were utilized to establish xenografts in athymic mice to investigate the effect of NOX1 silencing on tumor growth and gene expression in vivo. Significant decrease was measured in the volume of forming tumors. The stable clones and corresponding xenografts were analyzed on microarray. The microarray data was validated with real-time PCR and western-blot analysis demonstrating the inhibition of genes important in cell cycle regulation and angiogenesis. The results of this study show silencing NOX1 levels of generated ROS decreased, the tumor formation attenuated in vivo suggesting NOX1 may be a therapeutic target for colon cancer. Experiment Overall Design: We have found that NOX1 over-expression in colon cancer cell lines as well as surgical samples suggests a role in colon cancer. We identified unique target sequences of siRNAs for post-transcriptional silencing of NOX1. Gene specific and scrambled (control) sequences carrying the U6 promoter/shRNA cassettes were cloned into a GFP expression vector. Stable clones were selected based on NOX1 expression after transient transfection of HT-29 cells. HT-29 parental cells, clone SA (scrambled) and clone 6A (gene specific) were utilized to establish xenografts in athymic mice to investigate the effect of NOX1 silencing on tumor growth and gene expression in vivo. A significant decrease was measured in the volume of tumors formed. The stable clones and corresponding xenografts were analyzed on microarray. The microarray data was validated with real-time PCR and western-blot analysis demonstrating the inhibition of genes important in cell cycle regulation and angiogenesis. The results of this study show silencing NOX1 levels of generated ROS decreased, the tumor formation attenuated in vivo suggesting NOX1 may be a therapeutic target for colon cancer.
2008-06-13 | E-GEOD-4561 | biostudies-arrayexpress
Project description:CD38 expression is an important prognostic marker in CLL with high levels of CD38 associated with shorter overall survival. In this study, we used gene expression profiling and protein analysis of highly purified cell-sorted CD38+ and CD38- chronic lymphocytic leukemia cells to elucidate a molecular basis for the association between CD38 expression and inferior clinical outcome. Paired CD38+ and CD38- CLL cells derived from the same patient were shown to be monoclonal by VH gene sequencing but despite this, CD38+ CLL cells possessed a distinct gene expression profile when compared with their CD38- sub-clones. Keywords: Sub-clonal analysis of CLL cells derived from the same leukemia sample
2006-11-23 | GSE6321 | GEO
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
Project description:We collected three timepoint blood samples from a CLL patient underwent BTK inhibitor treatment. We performed single cell RNA sequencing on these samples to track expression heterogeneity of malignant B-cell populations over time.
2021-10-22 | GSE186150 | GEO
Project description:B cell chronic lymphocytic leukemia - A model with immune response
Seema Nanda 1, , Lisette dePillis 2, and Ami Radunskaya 3,
1.
Tata Institute of Fundamental Research, Centre for Applicable Mathematics, Bangalore 560065, India
2.
Department of Mathematics, Harvey Mudd College, Claremont, CA 91711
3.
Department of Mathematics, Pomona College, Claremont, CA, 91711, United States
Abstract
B cell chronic lymphocytic leukemia (B-CLL) is known to have substantial clinical heterogeneity. There is no cure, but treatments allow for disease management. However, the wide range of clinical courses experienced by B-CLL patients makes prognosis and hence treatment a significant challenge. In an attempt to study disease progression across different patients via a unified yet flexible approach, we present a mathematical model of B-CLL with immune response, that can capture both rapid and slow disease progression. This model includes four different cell populations in the peripheral blood of humans: B-CLL cells, NK cells, cytotoxic T cells and helper T cells. We analyze existing data in the medical literature, determine ranges of values for parameters of the model, and compare our model outcomes to clinical patient data. The goal of this work is to provide a tool that may shed light on factors affecting the course of disease progression in patients. This modeling tool can serve as a foundation upon which future treatments can be based.
Keywords: NK cell, chronic lymphocytic leukemia, mathematical model, T cell., B-CLL.
2020-01-09 | MODEL2001090002 | BioModels