Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA328592 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Comparison of CLL and MCL primary cells obtained from a patient with MCL variant Richter syndrome
2016-07-13 | GSE84286 | GEO
Project description:Gene expression analysis in Epstein-Barr virus negative DLBCL samples obtained from patients with Richter syndrome, lymphocytes from CLL patients and epstein-Barr virus positive DLBCL cell lines derived after CLL tumors xenotransplantation
2020-08-29 | GSE103265 | GEO
Project description:Richter syndrome (RS) occurs in up to 15% of patients with chronic lymphocytic leukemia (CLL). While RS, usually represented by the histologic transformation to a diffuse large B-cell lymphoma (DLBCL), is associated with a very poor outcome, especially when clonally related to the pre-existing CLL, mechanisms leading to RS have not been clarified yet. To better understand the pathogenesis of RS, we analyzed a series of cases including: 59 RS, 28 CLL-phase of RS, 315 CLL and 127 de novo DLBCL. RS demonstrated a genomic complexity intermediate between CLL and DLBCL. Cell cycle deregulation via inactivation of TP53 and of CDKN2A was a main mechanism in the histologic transformation from CLL-phase, being present in approximately half of the cases, and affected the outcome of the RS patients. A second major subgroup was characterized by the presence of trisomy 12 and comprised one third of the cases. While RS shared some of the lesions seen in de novo DLBCL, its genomic profile was clearly separate. The CLL-phase preceding RS had not a generalized increase in genomic complexity when compared with untransformed CLL, but it presented clear differences in the frequency of specific genetic lesions. Genomic profiling of Richter-syndrome Chronic Lymphocytic Leukemia
2013-09-20 | E-GEOD-50252 | biostudies-arrayexpress
Project description:The two B-cell non-Hodgkin lymphoma (NHL) entities chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL) show recurrent chromosomal gains of 3q25 q29, 12q13 q14 and 18q21-q22. The pathomechanisms affected by these aberrations are not understood. The aim of this study was to identify genes, located within these gained regions, which control cell death and cell survival of MCL and CLL cancer cells. Blood samples from 24 CLL and 6 MCL patients as well as 6 cell lines representing both malignancies were analyzed by gene expression profiling. By comparison of genomic DNA and gene expression, 72 candidate genes were identified. We performed a limited RNAi screen with these candidates in order to identify genes affecting cell survival. CCDC50, SERPINI2 and SMARCC2 mediated a reduction of cell viability in primary CLL cells as well as in cell lines. Gene knock down and a NFkB reporter gene assay revealed that CCDC50 is required for survival in MCL and CLL cells and controls NFkB signaling. This SuperSeries is composed of the SubSeries listed below.
2010-06-03 | GSE16413 | GEO
Project description:Protective interactions with bystander cells in micro-environmental niches such as lymph nodes (LNs) contribute to survival and therapy resistance of chronic lymphocytic leukemia (CLL) cells. This is caused by a shift in expression of BCL-2 family members. Pro-survival proteins BCL-XL, BFL-1, and MCL-1 are upregulated by LN-residing T cells through CD40L interaction, presumably via NF-κB signaling. Macrophages also reside in the LN, and are assumed to provide important supportive functions for CLL cells. However, if and how macrophages are able to induce survival is incompletely known. We first established that macrophages induced survival due to an exclusive upregulation of MCL-1. Next, we investigated the mechanism underlying MCL-1 induction by macrophages in comparison with CD40L. Genome-wide expression profiling of in vitro macrophage- and CD40L-stimulated CLL cells indicated activation of the PI3K-AKT-mTOR pathway, which was confirmed in ex vivo CLL LN material. Inhibition of PI3K-AKT-mTOR signaling abrogated MCL-1 upregulation and survival by macrophages as well asCD40 stimulation. MCL-1 can be regulated at multiple levels, and we established that AKT leads to increased MCL-1 translation, but does not affect MCL-1 transcription or protein stabilization. Furthermore, among macrophage-secreted factors that could activate AKT, we found that induction of MCL-1 and survival critically depended on C-C Motif Chemokine Receptor-1 (CCR1). In conclusion, this study indicates that two distinct micro-environmental factors, CD40L and macrophages, signal via CCR1 to induce AKT activation resulting in translational stabilization of MCL-1, and hence can contribute to CLL cell survival.
2017-02-11 | GSE94801 | GEO
Project description:We evaluated 13 B-PLL patient, 7 of whom were t(11;14)-positive (B-PLL+), and compared them with MCL and CLL patients.
2014-05-29 | E-MTAB-1991 | biostudies-arrayexpress
Project description:Functional studies to investigate gene mutations recurrent in B cell lymphoma have been hampered by the inability to genetically manipulate primary cells, attributed to low transduction efficacy and procedure-associated toxicity. Alternative approaches utilize cell lines and mouse models, which often only poorly represent the genomic complexity and biology of the primary malignancy. To overcome these limitations, we have developed a method to retrovirally transfer genes into primary malignant B cells with high transduction efficacy and minimal toxicity. Using this method, we investigated the functions of NOTCH1, the most commonly mutated gene in CLL, by generating isogenic primary tumor cells from patients with Chronic Lymphocytic Leukemia (CLL) and Mantle Cell Lymphoma (MCL), differing only in their expression of NOTCH1. Our data demonstrate that NOTCH1 facilitates immune escape of malignant B cells by up-regulating PD-L1, partly dependent on autocrine interferon-g signaling. In addition, NOTCH1 causes silencing of the entire HLA-class II locus via suppression of the transcriptional co-activator CIITA. These NOTCH1-mediated immune escape mechanisms are associated with the expansion of CD4+ T cells in vivo, further contributing to the poor clinical outcome of NOTCH1-mutated CLL and MCL
2022-08-26 | PXD024112 | Pride
Project description:Microarray-based gene expression analysis identified genes differentially expressed in 6 MCL and 18 CLL patient samples compared in independent analyses to CD19 selected healthy donor B-cell samples.
2010-06-03 | GSE16411 | GEO
Project description:The JAK1/2 inhibitor ruxolitinib is a cornerstone of management for some subsets of BCR-ABL negative myeloproliferative neoplasms (MPNs), but some patients respond suboptimally to ruxolitinib.Here, we evaluated the efficacy of micheliolide (MCL) alone or in combination with ruxolitinib in JAK2V617F mutated MPN cell lines, MPN patient primary samples and Jak2V617F knock-in mouse model and found that MCL was able to exert effective therapeutic effects in MPNs. To gain insights of the molecular mechanisms by which MCL exerts effects, we then performed gene expression profiling analysis using data obtained from RNA-seq of UKE1 cells following treatment with MCL and/or ruxolitinib.
2022-09-02 | GSE212305 | GEO
Project description:Background:A subset of hematological cancer patients is refractory to treatment or suffer relapse, due in part to minimal residual disease, whereby some cancer cells survive treatment via microenvironment interaction. Cell-adhesion mediated drug resistance is an important mechanism, whereby cancer cells receive survival signals via interaction with e.g. stromal cells. No genome-wide studies of in vitro systems have yet been performed to compare gene expression in different cell subsets within a co-culture and cells grown separately. Results: Using RNAseq and species-specific read mapping, we compared transcript levels in human Jeko-1 mantle cell lymphoma (MCL) cells stably adhered to stromal cells or in suspension within a co-culture and in separate culture as well as mouse MS-5 stromal cells in co-culture or in separate culture. 1050 differentially expressed transcripts in adherent MCL cells identified 24 functional categories that together represent four main functional themes, anti-apoptosis, B-cell signaling, cell adhesion/migration and early mitosis. Comparison with previous MCL and chronic lymphocytic leukemia (CLL) patient data identified 116 genes that are differentially regulated in all three studies. From these genes we suggest a gene signature (CCL3, CCL4, DUSP4, ETV5, ICAM1, IL15RA, IL21R, IL4I1, MFSD2A, NFKB1, NFKBIE, SEMA7A, TMEM2) characteristic of cells undergoing cell-adhesion mediated microenvironment signaling in MCL/ CLL cells. Conclusions: The model system developed and characterized here together with suggested signature genes can be used in future studies of pathways that mediate increased cancer cell survival and drug resistance mechanisms.
2018-06-12 | GSE99501 | GEO