Project description:Chronic lymphocytic leukemia (CLL) is the most frequent leukemia in Western countries. The main genetic alterations associated to this disease are loss of 13q14, loss of 11q23, trisomy 12 and, less frequently, 17p13 losses, and are routinely studied using fluorescence in situ hybridization. These genomic aberrations have been demonstrated to be important independent predictors of disease progression in CLL and their detection currently has a direct implication in the treatment strategy of the patients. It has been widely demonstrated that array-based karyotyping clearly detects DNA gains and losses and allows the identification of CLL abnormalities not included in the standard FISH panel. We have here established and tested an oligonucleotide-based array platform for the diagnosis of CLL that interrogates the most relevant chromosomal regions related with the disease and may help in the differential diagnosis between CLL and other small B-cell leukemias and may be used as a powerful prognosis tool to stratify the CLL patients. Copy number analysis using Custom Agilent 60K was performed on 47 chronic lymphocytic Leukemia patients with sex-matched control DNAs
Project description:Chronic lymphocytic leukemia (CLL) is the most frequent leukemia in Western countries. The main genetic alterations associated to this disease are loss of 13q14, loss of 11q23, trisomy 12 and, less frequently, 17p13 losses, and are routinely studied using fluorescence in situ hybridization. These genomic aberrations have been demonstrated to be important independent predictors of disease progression in CLL and their detection currently has a direct implication in the treatment strategy of the patients. It has been widely demonstrated that array-based karyotyping clearly detects DNA gains and losses and allows the identification of CLL abnormalities not included in the standard FISH panel. We have here established and tested an oligonucleotide-based array platform for the diagnosis of CLL that interrogates the most relevant chromosomal regions related with the disease and may help in the differential diagnosis between CLL and other small B-cell leukemias and may be used as a powerful prognosis tool to stratify the CLL patients.
Project description:Chronic lymphocytic leukemia (CLL) is the most frequent leukemia in Western countries. The main genetic alterations associated to this disease are loss of 13q14, loss of 11q23, trisomy 12 and, less frequently, 17p13 losses, and are routinely studied using fluorescence in situ hybridization. These genomic aberrations have been demonstrated to be important independent predictors of disease progression in CLL and their detection currently has a direct implication in the treatment strategy of the patients. It has been widely demonstrated that array-based karyotyping clearly detects DNA gains and losses and allows the identification of CLL abnormalities not included in the standard FISH panel. We have here established and tested an oligonucleotide-based array platform for the diagnosis of CLL that interrogates the most relevant chromosomal regions related with the disease and may help in the differential diagnosis between CLL and other small B-cell leukemias and may be used as a powerful prognosis tool to stratify the CLL patients.
Project description:This dataset includes chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), follicular lymphoma (FL), mantle cell lymphoma (MCL), and marginal zone lymphoma (MZL) cases reviewed for pathology consensus at the University Health Network. Also included are challenging cases of small B-cell lymphomas without pathology consensus. Methylation array profiling was performed using the Infinium MethylationEPIC array platform. Unprocessed IDAT files and matrix with beta values (beta_TGL51_illumina_annot_geo.txt) are provided.
Project description:THis is a simple ordinary differential equation model describing chemoimmunotherapy of chronic lymphocytic leukemia, including descriptions of the combinatorial effects of chemotherapy and adoptive cellular immunotherapy.
Project description:Screening for gene copy-number alterations (CNAs) has improved by applying genome-wide microarrays, where SNP arrays also allow analysis of loss of heterozygozity (LOH). We here analyzed 10 chronic lymphocytic leukemia (CLL) samples using four different high-resolution platforms: BAC arrays (32K), oligonucleotide arrays (185K, Agilent), and two SNP arrays (250K, Affymetrix and 317K, Illumina). Cross-platform comparison revealed 29 concordantly detected CNAs, including known recurrent alterations, which confirmed that all platforms are powerful tools when screening for large aberrations. However, detection of 32 additional regions present in 2-3 platforms illustrated a discrepancy in detection of small CNAs, which often involved reported copy-number variations. LOH analysis revealed concordance of mainly large regions, but showed numerous, small nonoverlapping regions and LOH escaping detection. Evaluation of baseline variation and copy-number ratio response showed the best performance for the Agilent platform and confirmed the robustness of BAC arrays. Accordingly, these platforms demonstrated a higher degree of platform-specific CNAs. The SNP arrays displayed higher technical variation, although this was compensated by high density of elements. Affymetrix detected a higher degree of CNAs compared to Illumina, while the latter showed a lower noise level and higher detection rate in the LOH analysis. Large-scale studies of genomic aberrations are now feasible, but new tools for LOH analysis are requested. 10 chronic lymphocytic leukemia (CLL) samples was analyzed using four different high-resolution platforms: 32K BAC arrays, 185K Agilent oligonucleotide arrays, 250K Affymetrix SNP arrays and 317K Illumina SNP arrays.
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.
Project description:Genomic profiles of CLL (Chronic Lymphocytic Leukemia) patients. 11 CLL patients were selected for detection of genomic aberrations, 8 patients with atypical CLL and 3 patients with typical CLL.