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GSE63790
Homo sapiens
20 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Hairy 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.
Publication Title
BRAF inhibitors reverse the unique molecular signature and phenotype of hairy cell leukemia and exert potent antileukemic activity.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
We 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.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
To 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.
Publication Title
Leukemic marrow infiltration reveals a novel role for Egr3 as a potent inhibitor of normal hematopoietic stem cell proliferation.
Sample Metadata Fields
Age, Specimen part, Disease, Disease stage, Time
View Samples- Homo sapiens
- 12 Downloadable Samples
Illumina HiSeq 2000
Description
Day 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+
Publication Title
No associated publication
Sample Metadata Fields
Sex, Specimen part, Disease, Cell line, Treatment
View Samples- Homo sapiens
- 139 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part, Disease, Disease stage, Subject
View Samples- Homo sapiens
- 118 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The genetic and genomic background of multiple myeloma patients achieving complete response after induction therapy with bortezomib, thalidomide and dexamethasone (VTD).
Sample Metadata Fields
Specimen part, Disease, Disease stage, Subject
View Samples- Homo sapiens
- 139 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The 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.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 106 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
A subanalysis of the GIMEMA-MMY-3006 trial was performed to characterize treatment-emergent peripheral neuropathy (PN) in patients randomized to thalidomide-dexamethasone (TD) or bortezomib-TD (VTD) before and after double autologous transplantation (ASCT) for multiple myeloma (MM). 236 patients randomized to VTD and 238 to TD were stratified according to the emergence of grade 2 PN. Gene expression profiles (GEP) of CD138+ plasma cells were analyzed from 122 VTD-treated patients. The incidence of grade 2 PN was 35% in the VTD arm and 10% in the TD arm (p<0.001). PN resolved in 88% and 95% of patients in VTD and TD groups, respectively. Rates of complete/near complete response, progression-free and overall survival were not adversely affected by emergence of grade 2 PN. Baseline characteristics were not risk factors for PN, while GEP analysis revealed the deregulated expression of genes implicated in cytoskeleton rearrangement, neurogenesis and axonal guidance. In conclusion, in comparison with TD, incorporation of VTD into ASCT was associated with a higher incidence of PN which, however, was reversible in most of the patients and did not adversely affect their outcomes nor their ability to subsequently receive ASCT. GEP analysis suggests an interaction between myeloma genetic profiles and development of VTD-induced PN.
Publication Title
Bortezomib- and thalidomide-induced peripheral neuropathy in multiple myeloma: clinical and molecular analyses of a phase 3 study.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 118 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The prime focus of the current therapeutic strategy for Multiple Myeloma (MM) is an early and deep tumour burden reduction; this characterizes and defines the complete response (CR). To date, no description of the characteristics of the plasma cells (PC) prone to achieve CR has been reported. This study aimed at the molecular characterization of PC derived from MM patients who achieved CR after bortezomib-thalidomide-dexamethasone (VTD) first line therapy.
Publication Title
The genetic and genomic background of multiple myeloma patients achieving complete response after induction therapy with bortezomib, thalidomide and dexamethasone (VTD).
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 31 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Thalidomide-dexamethasone (TD) combination is an effective induction therapy for newly diagnosed multiple myeloma patients, candidates for subsequent autologous stem cell transplantation (ASCT). Since maximization of tumor response before ASCT may favorably affect the clinical outcomes, we designed a study to identify a gene expression profile (GEP) signature predictive of attainment of complete response to TD induction therapy. CD138+ bone marrow samples obtained at diagnosis from 112/311 patients were analyzed. Two subsequent time phases were planned. Firstly, a GEP supervised analysis, performed on a training set of 32 patients, allowed to identify 157 probe sets differentially expressed in complete responder + near complete responder (CR+nCR) versus partial responder patients. Than, we generated an 8-gene GEP signature predicting at diagnosis the probability to achieve CR+nCR to TD induction therapy. The performance of this assay was subsequently validated in an 80 patients training set. The 8-gene signature provide a negative predictive value of 93% and a positive predictive value of 44%. The 8 genes were down-regulated in patients who achieved at least a nCR. These results could be an important first step to adopting a diagnostic assay, used to determine, at diagnosis, patients who will respond more favourably to a particular treatment strategy.
Publication Title
Correlation between eight-gene expression profiling and response to therapy of newly diagnosed multiple myeloma patients treated with thalidomide-dexamethasone incorporated into double autologous transplantation.
Sample Metadata Fields
Age, Specimen part, Disease, Disease stage
View Samples