Hedgehog pathway analysis in both CD138+ and B-cells obtained from newly diagnosed Multiple Myeloma patients
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ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Carolina Terragna
PROVIDER: E-GEOD-69000 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project 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. Here, we report on a high-throughput transcriptome study of gene expression profiles in newly diagnosed MM patients analyzed both in the CD138+ plasmacell fraction and in the CD19+ B cells compartment. Resulted data demonstrated that Hedgehog pathway, and in particular, a 10 HH-genes signature was heterogeneously expressed among MM patients, both in mature plasmacells and also in B cells at transcriptional level. Interestingly, this signature divide patients in two subgroups, and it seems that exists a sort of âying-yang effectâ between mature and immature cell compartments that are tightly regulate in order to express this relevant self-renewal pathway according to their maturation state. 144 samples have been analyzed: 126 BM-CD138+, 7 BM-B cells and 11 PBL-B cells; the homogeneity of samples has been ensured by the immunomagnetic enrichment procedure: only >90% pure cells have been employed.
2016-05-31 | E-GEOD-68891 | biostudies-arrayexpress
Project 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. One hundred and eighteen MM primary tumours obtained from homogeneously treated patients were globally profiled both for gene expression and for single nucleotide polymorphism genotype. Genomic results were used to obtain a predictor of sensitivity to VTD induction therapy, as well as to describe both the transcription and the genomic profile of PC derived from patients with MM who will respond optimally to primary induction therapy. By analysing the gene profiles of CR patients, we identified a 5-gene signature predicting CR with an overall median accuracy of 75% (range: 72%-85%). In addition, we highlighted the differential expression of a series of genes, whose deregulation, accordingly to their reported functions, might explain the CR patientsâ?? sensitivity to VTD therapy. We also showed that a small copy number loss, covering 606Kb on chromosome 1p22.1 was the most significantly associated with CR patients. The study provides insights into the genomic landscape of PC obtained from newly diagnosed MM patients achieving CR after VTD and shows that patients might be accurately stratified according to their sensitivity to VTD. Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from cryopreserved diagnostic CD138+ cell fractions obtained from bone marrow samples.
2015-12-31 | E-GEOD-69028 | biostudies-arrayexpress
Project 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. One hundred and eighteen MM primary tumours obtained from homogeneously treated patients were globally profiled both for gene expression and for single nucleotide polymorphism genotype. Genomic results were used to obtain a predictor of sensitivity to VTD induction therapy, as well as to describe both the transcription and the genomic profile of PC derived from patients with MM who will respond optimally to primary induction therapy. By analysing the gene profiles of CR patients, we identified a 5-gene signature predicting CR with an overall median accuracy of 75% (range: 72%-85%). In addition, we highlighted the differential expression of a series of genes, whose deregulation, accordingly to their reported functions, might explain the CR patientsâ sensitivity to VTD therapy. We also showed that a small copy number loss, covering 606Kb on chromosome 1p22.1 was the most significantly associated with CR patients. The study provides insights into the genomic landscape of PC obtained from newly diagnosed MM patients achieving CR after VTD and shows that patients might be accurately stratified according to their sensitivity to VTD. 118 samples have been analyzed; the homogeneity of samples has been ensured by the immunomagnetic enrichment procedure: only >90% pure CD138+ cells have been employed. Response to vtd therapy (provided in each sample record); CR: complete response nCR: near complete response VGPR: Very good partial response PR: partial response SD: Stable disease
2015-12-31 | E-GEOD-68871 | biostudies-arrayexpress
Project 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 M-bM-^IM-%2 PN. Gene expression profiles (GEP) of CD138+ plasma cells were analyzed from 122 VTD-treated patients. The incidence of grade M-bM-^IM-%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 M-bM-^IM-%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. 120 samples have been analyzed; the homogeneity of samples has been ensured by the immunomagnetic enrichment procedure: only >90% pure CD138+ cells have been employed.
2014-12-23 | E-GEOD-58133 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2015-12-31 | E-GEOD-69029 | biostudies-arrayexpress
Project description:Purpose: Because dexamethasone remains a key component of myeloma therapy, we wished to examine the correlation of baseline and relapse expression levels of the glucocorticoid receptor gene NR3C1 with other clinical features. Experimental Design: We investigated the clinical impact of gene expression profiling (GEP)–derived expression levels of NR3C1 in 351 patients with GEP data available at baseline and in 130 with data available at relapse, among 668 subjects accrued to Total Therapy 2 (TT2). The effect of the expression of NR3C1 at baseline (previously published under GSE2685) and at relapse was analyzed in the context of treatment (thalidomide vs. no thalidomide) and other clinical parameters.
2012-11-05 | E-GEOD-38627 | biostudies-arrayexpress
Project description:This Series represents the gene expression profiles of patients with multiple myeloma who have been treated previously. In brief, Total Therapy 6 (TT6) is an open label phase 2 protocol for patients with symptomatic multiple myeloma, who had been treated with more than one cycle of prior therapy excluding autologous hematopoietic stem cell transplant. This protocol was approved by the institutional review board on March 25, 2009 (IRB#108053). The TT6 treatment regimen consists of induction therapy with Melphalan/Bortezomib/Thalidomide/Dexamethasone/Cisplatin/Doxorubicin/Cyclophosphamide/Etoposide (M-VTD-PACE) followed by a high dose M-VTD-PACE based tandem transplant. Maintenance therapy consists of Bortezomib/Lenalidomide/Dexamethasone alternating with Borteomib/Melphalan/Dexamethasone every months for 3 years. We analyzed CD138+ selected cells of previously treated MM patients by microarray.
2015-01-20 | E-GEOD-57317 | biostudies-arrayexpress
Project description:ArrayCGH profiling and examination of IgH disruption by FISH on two myeloma B-cell lineage subpopulations: CD138+ and CD19+ to confirm existence of abnormal bone marrow B-cell subset contaning genetic background for primary oncogenic events.
2013-12-07 | E-MTAB-1401 | biostudies-arrayexpress
Project description:Samples in this series are pre-treatment bone marrow aspirates from multiple myeloma patients. Experiment Overall Design: Samples in this series are: Experiment Overall Design: 1. CD-138-selected plasma cells from bone marrow of patients with newly diagnosed multiple myeloma subsequently treated with high dose therapy and stem cell transplants termed Total Therapy 2 (pre-treatment TT2) Experiment Overall Design: 2. CD-138-selected plasma cells from bone marrow of patients with newly diagnosed multiple myeloma subsequently treated with Total Therapy 3 (pre treatment TT3). Experiment Overall Design: Overall Design: Experiment Overall Design: Gene expression signatures were used to: 1) develop unsupervised hierarchical cluster classes; 2) establish links with outcome following stem cell transplantation
2008-06-13 | E-GEOD-2658 | biostudies-arrayexpress
Project description:Samples in this series are pre-treatment bone marrow aspirates from multiple myeloma patients Experiment Overall Design: Samples in this series are: Experiment Overall Design: 1. CD-138-selected plasma cells from bone marrow of newly diagnosed multiple myeloma patients susequently treated with Total Therapy 2 (pre-treatment TT2) Experiment Overall Design: 2. CD-138-selected plasma cells from bone marrow of newly diagnosed multiple myeloma patients susequently treated with Total Therapy 3 (pre treatment TT3). Experiment Overall Design: Overall Design: Experiment Overall Design: Baseline gene expression signatures were used to: 1) develop unsupervised hierarchical cluster classes; 2) establish links with outcome following stem cell transplantation
2008-04-07 | E-GEOD-4204 | biostudies-arrayexpress