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Expression data from BM-CD138+, obtained from newly diagnosed Multiple Myeloma patients [response to VTD therapy]

ABSTRACT: 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 patients’ 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE68871 | GEO | 2015/12/31

SECONDARY ACCESSION(S): PRJNA283982

REPOSITORIES: GEO

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Affymetrix SNP array data from BM-CD138+, obtained from newly diagnosed Multiple Myeloma patients [response to VTD therapy]

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 patients’ 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.

2015-12-31 | GSE69028 | GEO

Expression data from BM-CD138+, obtained from newly diagnosed Multiple Myeloma patients [response to VTD therapy]

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

Affymetrix SNP array data from BM-CD138+, obtained from newly diagnosed Multiple Myeloma patients [response to VTD therapy]

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

Expression data from BM-CD138+, obtained from newly diagnosed Multiple Myeloma patients

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 ≥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.

2014-12-23 | GSE58133 | GEO

Expression data from BM-CD138+, obtained from newly diagnosed Multiple Myeloma patients

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.

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Gene expression profiles of patients with multiple myeloma who have been treated previously

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

Expression data from CD138+ cells obtained from MM patients at diagnosis

Project 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. This series of microarray experiments contains the gene expression profiles of purified plasma cells (PCs) obtained from 32 newly diagnosed multiple myeloma (MM). PCs were purified from bone marrow specimens, using CD138 immunomagnetic microbeads. The purity of the positively selected PCs was assessed by flow cytometry and was > 90% in all cases. 5 micrograms of total RNA was processed and hybridized to the Affymetrix HG U133 Plus 2.0 GeneChip following the manufacturer's instructions.

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Project 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.

2013-06-01 | GSE16791 | GEO

CD138+ expression and genomic profile obtained from newly diagnosed Multiple Myeloma patients up-front treated with VTD induction therapy

Project description:CD138+ expression and genomic profile obtained from newly diagnosed Multiple Myeloma patients up-front treated with VTD induction therapy

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Gene expression profiles of patients with multiple myeloma who have been treated previously

2015-01-20 | GSE57317 | GEO