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Recombinant IL-1 RA in human Chronic lymphocytic leukemia cells in vitro

ABSTRACT: Inflammatory factors that activate NFkB play an important role in the pathogenesis of chronic lymphocytic leukemia (CLL) but are not addressed specifically by current therapies. Interleukin-1 (IL-1) is a master-regulator of inflammation that is inhibited safely in humans by the IL-1 receptor antagonist anakinra. Anakinra (K) was found to inhibit NFkB activity in CLL cells in an IL-1 receptor independent manner and had properties of an intracellular anti-oxidant in vitro.

ORGANISM(S): Homo sapiens

PROVIDER: GSE236552 | GEO | 2023/10/04

REPOSITORIES: GEO

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A phase I trial of the IL1-receptor antagonist anakinra in previously untreated CLL patients at risk for progression

Project description:Inflammatory factors that activate NFkB play an important role in the pathogenesis of chronic lymphocytic leukemia (CLL) but are not addressed specifically by current therapies. Interleukin-1 (IL-1) is a master-regulator of inflammation that is inhibited safely in humans by the IL-1 receptor antagonist anakinra. Anakinra was found to inhibit NFkB activity in CLL cells in an IL-1 receptor independent manner and had properties of an intracellular anti-oxidant in vitro. A phase I dose-escalation trial in 11 previously untreated CLL patients (NCT04691765) indicated anakinra was safe at doses up to 400 mg daily and produced transient clinical responses associated with down-regulation of NFkB and oxidative stress in circulating CLL cells in vivo. However, type 1 interferon (IFN)-signaling and c-MYC-regulated genes and proteins were induced at the same time.

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Identification of interleukin-4 (IL-4) targets in chronic lymphocytic leukemia (CLL)

Project description:Gene expression profiles of CLL cells and normal B cells (NBC) treated for 18 hr with 10 ng/ml IL-4, compared with culture with nothing (Ctrl) and the basal (Pre) samples. Patient CLL01 was also treated with IL-4 plus 5 mg/ml ERK activation inhibitor peptide I, or IL-4 plus 10 ÂµM NFkB activation inhibitor, and IL-4 plus 100 mg/ml cyclic-pifithrin-Î± 23 CLL patients (10 Pre samples, 23 Ctrl samples, 23 IL-4 samples, 1 IL-4 plus ERK inhibitor sample, 1 IL-4 plus NFkB inhibitor sample, 1 IL-4 plus Pifithrin sample), 13 NBC (10 Pre samples, 10 Ctrl samples, 13 IL-4 samples)

2014-10-06 | E-GEOD-55288 | biostudies-arrayexpress

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Project description:CLL cells obtained from patients with CLL were treated with MLN4924 to determine whether NFkB transcription targets were affected by the drug.

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Identification of interleukin-4 (IL-4) targets in chronic lymphocytic leukemia (CLL)

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Project description:CLL cells obtained from patients with CLL were treated with MLN4924 to determine whether NFkB transcription targets were affected by the drug. CLL cells were treated with 1 microM MLN4924 or vehicle control for 24 hours. Cells were collected by centrifugation and B-cell were purified using negative selection (B cell purification Kit, Multenyi Biotech). RNA was isolated and submitted for Gene expression analysis

2013-03-05 | E-GEOD-44864 | biostudies-arrayexpress

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Gene knock down studies revealed CCDC50 as candidate gene in mantle cell lymphoma and chronic lymphocytic leukemia

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IL-21 regulates the expression of chemokine genes in B-chronic lymphocytic leukemia

2013-09-01 | GSE42158 | GEO

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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

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