Evaluation of pretreatment gene expression profiling features in elderly CLL patients; correlation with clinical outcome
No associated publication
Sex, Age, Specimen part
View SamplesWe describe 9 CLL patients who underwent a spontaneous clinical regression. CD38 and ZAP-70 were negative in all cases. Immunoglobulin heavy chain variable region (IgVH) genes, mutated in all 7 evaluable patients, were restricted to the VH3 family in 6, with the usage of VH3-30 gene in 2. The light chain variable region genes were mutated in 6/8 cases, with the usage of V4-1 gene in 3. Microarray analysis of CLL cells revealed a distinctive genomic profile. The number of activated T lymphocytes expressing IFN-, TNF- and IL-4 was similar between CLL in spontaneous regression and healthy individuals.
Spontaneous regression of chronic lymphocytic leukemia: clinical and biologic features of 9 cases.
Specimen part
View SamplesSince the role of cord blood (CB) regulatory T cells (Tregs) for the suppression of the allogeneic T-cell response is under investigation, we analyzed and compared the functional properties and gene expression profile of Tregs expanded from CB units or from the peripheral blood (PB) of helathy donors. Tregs were purified from 23 CB units and from the PB of 13 donors and expanded for 6 days with anti-CD3, anti-CD28 and IL-2. Immunophenotypic analyses were performed, and suppressor activity of expanded Tregs was measured in mixed lymphocyte reaction (MLR) cultures. The IL-10 production capacity was tested and gene expression profile experiments were performed on 6 Tregs from PB and 4 from CB. CB and PB Tregs had similar immunophenotypic features. Tregs from CB presented a higher expansion capacity and genomic characterization showed in CB-derived Tregs a significant enrichments of genes involved in cell proliferation, chromatin modification and regulation of gene expression in CB-derived Tregs. All samples were positive for the Foxp3 gene and protein after expansion. CB and PB expanded Tregs exerted a comparable and potent suppressive function of MLR and presented a high in vitro IL-10 production capacity. Gene profile analysis also revealed for PB Tregs a significant enrichments of genes involved in the adaptive immune response.
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Specimen part
View SamplesDay 3 mesoderm generated from H1 PSCs by differentiation protocol found in:"Sturgeon CM, Ditadi A, Awong G, Kennedy M, Keller G. Wnt Signaling Controls the Specification of Definitive and Primitive Hematopoiesis From Human Pluripotent Stem Cells. Nature biotechnology. 2014;32(6):554-561."Definitive hematopoiesis was specified using CHIR99021 treatment to agonize Wnt signaling and KDR+CD235a- mesoderm at Day 3 was FACS isolated. Primitive mesoderm was specified using IWP2 treatment to antagonize Wnt signaling and KDR+CD235a+ primitive mesoderm and KDR+CD235a- mesoderm was FACS isolated. There are 5 replicates of each sample type:CHIR CD235a-IWP CD235a-IWP CD235a+
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Sex, Specimen part, Disease, Cell line, Treatment
View SamplesHairy cell leukemia (HCL) shows unique clinico-pathological and biological features. HCL responds well to purine analogues but relapses are frequent and novel therapies are required. BRAF-V600E is the key driver mutation in HCL and distinguishes it from other B-cell lymphomas, including HCL-like leukemias/lymphomas (HCL-variant and splenic marginal zone lymphoma). The kinase-activating BRAF-V600E mutation also represents an ideal therapeutic target in HCL. Here, we investigated the biological and therapeutic importance of the activated BRAF-MEK-ERK pathway in HCL by exposing in vitro primary leukemic cells purified from 26 patients to clinically available BRAF (Vemurafenib; Dabrafenib) or MEK (Trametinib) inhibitors. Results were validated in vivo in samples from Vemurafenib-treated HCL patients within a phase-2 clinical trial. BRAF and MEK inhibitors caused, specifically in HCL (but not HCL-like) cells, marked MEK/ERK dephosphorylation, silencing of the BRAF-MEK-ERK pathway transcriptional output, loss of the HCL-specific gene expression signature, downregulation of the HCL markers CD25, TRAP and cyclin-D1, smoothening of leukemic cells' hairy surface, and, eventually, apoptosis. Apoptosis was partially blunted by co-culture with bone marrow stromal cells antagonizing MEK-ERK dephosphorylation. This protective effect could be counteracted by combined BRAF and MEK inhibition. Our results strongly support and inform the clinical use of BRAF and MEK inhibitors in HCL.
BRAF inhibitors reverse the unique molecular signature and phenotype of hairy cell leukemia and exert potent antileukemic activity.
Specimen part, Treatment, Subject
View SamplesWe used microarrays to evaluate the global programme of gene expression after Dox inducible Yamanaka factors ectopic expression and identified distinct classes of genes during this biological process in vivo.
No associated publication
Specimen part, Disease, Disease stage
View SamplesTo investigate the molecular basis for the reversible suppression of HSCs by leukemia, we sorted the CD45.1+LKS+ population from control or leukemic mice at day 7 and day 14 for gene expression profiling analysis.
Leukemic marrow infiltration reveals a novel role for Egr3 as a potent inhibitor of normal hematopoietic stem cell proliferation.
Age, Specimen part, Disease, Disease stage, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
No associated publication
Specimen part, Disease, Disease stage, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
The genetic and genomic background of multiple myeloma patients achieving complete response after induction therapy with bortezomib, thalidomide and dexamethasone (VTD).
Specimen part, Disease, Disease stage, Subject
View SamplesThe iperactivation of self-renewal mechanisms, like Hedgehog (HH) pathway, which govern the refuel of Multiple Myeloma neoplastic clone, is critical to relapse events. The bulk of current knowledge is mainly based on the CD138+ cells molecular characterization, but in the light of the recent evidences, which attributed growing relevance to immature precursor clones, we become aware that multiple myeloma disease heterogeneity have more deepen roots.
No associated publication
Specimen part, Disease, Disease stage
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