CD40 stimulation of chronic lymphocytic leukemia (CLL) cells
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ABSTRACT:
PROVIDER: PRJNA830901 | ENA |
REPOSITORIES: ENA
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Project description:In this experiment we in vitro activated CLL cells on a layer of fibroblasts expressing CD40L (3T40) or nothing (3T3) for 48 hours. After the 48 hours, cells were taken off the fibroblasts and sorted for viable CD19+ cells. Then we performed RNA sequencing.
2022-05-20 | GSE201341 | GEO
Project description:In this experiment we in vitro activated CLL cells on a layer of fibroblasts expressing CD40L (3T40) in the presence of 100 nM Dasatinib for 48 hours. After the 48 hours, cells were taken off the fibroblasts and sorted for viable CD19+ cells. Then we performed RNA sequencing.
2024-05-01 | GSE264554 | GEO
Project description:Many functional consequences of mutations on tumor phenotypes in chronic lymphocytic leukemia (CLL) are only partially known. This is in part due to a scarcity of information on the proteome of CLL. We profiled the proteome of 117 CLL samples with data-independent acquisition mass spectrometry (DIA-MS) and integrated the results with genomic, transcriptomic, functional data and clinical outcome. We found trisomy 12 and IGHV to be major determinants of proteome variation in CLL (1055 and 542 differential proteins FDR of 5%). Trisomy 12 was associated with limited protein abundance buffering. Protein complex analyses detected functional units involved in BCR/PI3K/AKT signaling in CLL with trisomy 12. We associated protein expression with response to anticancer drugs, and STAT2 protein expression emerged as a biomarker for the prediction of response to kinase inhibitors including BTK and MEK inhibitors. STAT2 protein levels were determined by gene dosage (trisomy 12), stabilization in a protein complex and linked to interferon signaling in CLL. This study highlights the emerging importance of protein abundance profiling in CLL biology.
2021-09-24 | PXD022198 | Pride
Project description:B-cell chronic lymphocytic leukemia (CLL) is a common type of leukemia, characterized by the progressive accumulation of CD5+ “mature” monoclonal B lymphocytes in peripheral blood, bone marrow and lymphoid tissues. Although circulating CLL cells are non-dividing cells, prone to spontaneous apoptosis, their progressive accumulation is the result of a dynamic balance between cell death and proliferation and a high turn-over rate has been related to a poor prognosis. Indeed, CLL cells are protected from apoptosis and proliferate in specific niches within the lymphoid tissues and the bone marrow. CLL cells show variable expression of IL-21R that can be up-regulated by cell activation via CD40. CD40-activated CLL cells phosphorylate STAT-1 and STAT-3 and undergo apoptosis in response to IL-21 stimulation. By gene-expression profiling we found out that IL-21 modulates the expression of several genes including cytokine and chemokine genes and genes involved in cell survival and apoptosis in CD40-activated CLL cells.
2013-09-01 | GSE42158 | GEO
Project description:Analysis of lncRNA expression in negatively selected pooled peripheral blood CLL samples compared to pooled peripheral blood normal B-cells with or without stimulation with CD40 ligand.
2016-10-04 | GSE87575 | GEO
Project description:The B-cell receptor (BCR) signaling is crucial for the pathophysiology of most leukemias and lymphomas originated from mature B lymphocytes and has emerged as a new therapeutic target, especially for chronic lymphocytic leukemia (CLL). However, the precise mechanisms by which BCR signaling controls neoplastic B-cell proliferation are ill characterized. This work was performed using primary leukemic cells of untreated patients at initial stage of CLL (Binet stage A / Rai 0) presenting biological characteristics of aggressive form of the disease (unmutated IGHV genes and ZAP70 protein expression). In order to mimic the primary leukemogenic step occurring in vivo, this study focused on the BCR-dependent proliferation of CLL cells induced ex vivo using anti-IgM, together with mandatory co-stimulating factors (CD40L, IL-4 and IL-21) (Schleiss, Sci Rep, 2019). Cell proliferation was objectivized by the emergence of proliferative clusters and the presence of more than 25% of CLL cells that did undergo division within the cell culture at day 6. To capture the specific actors of the proliferative response in these samples, we also included non-proliferating control CLL samples. Gene expression was analyzed by RNA-seq before stimulation (T0) and at the time points 1h, 1h30, 3h30, 6h30, 12h, 24h, 48h and 96h after cell stimulation (n=54 data points), the latest time points corresponding to the emergence of the proliferation clusters.
2021-05-12 | GSE130385 | GEO
Project description:In this experiment we in vitro activated T cells from CLL patients either in the presence or absence of their autologous CLL cells. After 48 hours of antiCD3/antiCD28 stimulation, the CD4 cells were FACS sorted from two condition and RNA sequencing was performed on these cells.
2022-09-26 | GSE193671 | GEO
Project description:B-cell chronic lymphocytic leukemia (CLL) is a common type of leukemia, characterized by the progressive accumulation of CD5+ “mature” monoclonal B lymphocytes in peripheral blood, bone marrow and lymphoid tissues. Although circulating CLL cells are non-dividing cells, prone to spontaneous apoptosis, their progressive accumulation is the result of a dynamic balance between cell death and proliferation and a high turn-over rate has been related to a poor prognosis. Indeed, CLL cells are protected from apoptosis and proliferate in specific niches within the lymphoid tissues and the bone marrow. CLL cells show variable expression of IL-21R that can be up-regulated by cell activation via CD40. CD40-activated CLL cells phosphorylate STAT-1 and STAT-3 and undergo apoptosis in response to IL-21 stimulation. By gene-expression profiling we found out that IL-21 modulates the expression of several genes including cytokine and chemokine genes and genes involved in cell survival and apoptosis in CD40-activated CLL cells. PBMCs were isolated from heparinized blood obtained from 13 untreated patients diagnosed with CLL on the basis of clinical and immunophenotypic criteria. PBMCs were isolated by Ficoll density gradient centrifugation and characterized by immunofluorescence and FACS analysis. When residual non B-cells exceeded 10%, B cells were enriched by negative selection with antibody-coated magnetic beads (CD2-beads, Dynal, Oslo, Norway) to obtain a >95% pure CD19+/CD5+ B cell population. B-CLL cells were pre-activated on adherent CD40L-transduced L cells for 48-36h and then stimulated with IL-21 or medium only for additional 18h. Total RNA was isolated from samples using TriZol (Invitrogen) reagent.
2013-09-01 | E-GEOD-42158 | biostudies-arrayexpress
Project description:The B-cell receptor (BCR) signaling is crucial for the pathophysiology of chronic lymphocytic leukemia (CLL). Although the BCR has recently emerged as a new therapeutic target the precise mechanisms by which BCR signaling controls neoplastic B-cell proliferation are still ill characterized. Here, by comparing proliferating vs. non-proliferating cells from aggressive CLL patients, we longitudinally characterized the transcriptional and proteomic response of CLL cells after BCR engagement ex vivo. Of the 5,733 genes and/or proteins which expression was modulated after BCR activation, we identified a CLL proliferative signature including 430 genes and 374 proteins. Mathematical modelling of this signature revealed a nested sub-regulatory network comprising transcription factors activated within hours after cell activation linked to proteins involved in cell proliferation days after stimulation. The mining of this core cellular program sustaining primary human cancer cells proliferation provides an evidence based-resource for innovative therapeutic perspectives.
2021-03-29 | PXD013573 | Pride
Project description:The B-cell receptor (BCR) signaling is crucial for the pathophysiology of chronic lymphocytic leukemia (CLL). Although the BCR has recently emerged as a new therapeutic target the precise mechanisms by which BCR signaling controls neoplastic B-cell proliferation are still ill characterized. Here, by comparing proliferating vs. non-proliferating cells from aggressive CLL patients, we longitudinally characterized the transcriptional and proteomic response of CLL cells after BCR engagement ex vivo. Of the 5,733 genes and/or proteins which expression was modulated after BCR activation, we identified a CLL proliferative signature including 430 genes and 374 proteins. Mathematical modelling of this signature revealed a nested sub-regulatory network comprising transcription factors activated within hours after cell activation linked to proteins involved in cell proliferation days after stimulation. The mining of this core cellular program sustaining primary human cancer cells proliferation provides an evidence based-resource for innovative therapeutic perspectives.
2021-09-08 | PXD013696 | Pride