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Impact of Gene Expression Profiling Based Risk Stratification in Patients with Myeloma Receiving Initial Therapy with Lenalidomide and Dexamethasone

ABSTRACT: Detection of specific chromosomal abnormalities by FISH and metaphase cytogenetics allows risk stratification in multiple myeloma (MM); however, gene expression profiling (GEP) based signatures may enable more specific risk categorization. We examined the utility of two GEP-based risk stratification systems among patients undergoing initial therapy with lenalidomide in the context of a phase 3 trial.

ORGANISM(S): Homo sapiens

PROVIDER: GSE31504 | GEO | 2011/08/26

SECONDARY ACCESSION(S): PRJNA145757

REPOSITORIES: GEO

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Impact of Gene Expression Profiling Based Risk Stratification in Patients with Myeloma Receiving Initial Therapy with Lenalidomide and Dexamethasone

Project description:Detection of specific chromosomal abnormalities by FISH and metaphase cytogenetics allows risk stratification in multiple myeloma (MM); however, gene expression profiling (GEP) based signatures may enable more specific risk categorization. We examined the utility of two GEP-based risk stratification systems among patients undergoing initial therapy with lenalidomide in the context of a phase 3 trial. The E4A03 clinical trial randomized patients with previously untreated MM to lenalidomide and either standard-dose dexamethasone. Baseline bone marrow samples were obtained from consenting patients. The marrow aspirates were subjected to a fully automated ROBOSEP cell separation system that utilizes immunomagnetic technology to positively select for CD 138+ cells. The purity of the sorting was confirmed by 3-color immunofluorescent slide based assessment on the sorted cells. The plasma cell gene expression proﬁles were analyzed using U133 Plus 2.0 array. All samples were run individually with no pooling. The GEP-70 signature was determined as previously described, using log2 transformed raw MAS 5.0 signals. The GEP15 classification was performed as previously described, with the patients in highest quartile for the risk score being considered as high risk.

2011-08-25 | E-GEOD-31504 | biostudies-arrayexpress

Affymetrix SNP array data for myelodysplastic syndrome with 5q deletion treated with lenalidomide

Project description:Lenalidome is a drug especially effective in low risk myelodysplastic syndromes (MDS) with isolated 5q deletion. However, 25% of the patients did not respond. TP53 mutations have been described to play a role in the disease progression, and karyotypic complexity also has an important impact in the outcome. We selected 53 MDS patients with 5q deletion and treated with lenalidomide and we studied by the following techniques: conventional G-banding cytogenetics (CC), single nucleotide polymorphism arrays (SNP-A) and sequencing, in order to assess their impact on treatment response and disease progression. Low karyotypic complexity (by CC), a high baseline platelet count (>280x103/L) and TP53 unmutated gene status are associated with the achievement of hematological response (P=0.005, P=0.008 and P=0.057, respectively). In a multivariate model, the most important predictors for lenalidomide failure are karyotypic complexity (P=0.014) and a platelet count below 280x103/L (P=0.042). Additionally, none of the TP53 mutated cases achieved complete cytogenetics response. Nevertheless, inclusion of defects by SNP-A did not allow for a better separation of responders and non responders. These findings constitute a useful reference data to be considered before lenalidomide treatment enrollment.

2013-07-01 | GSE35656 | GEO

Affymetrix SNP array data for myelodysplastic syndrome with 5q deletion treated with lenalidomide

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Gene expression profiles of nurse-like cells (NLCs) generated in vitro from chronic lymphocytic leukemia in presence of lenalidomide

Project description:NLCs were generated in vitro by culturing PBMCs from CLL patients for 10 days with/without the addition of 0.5 ÂµM lenalidomide. Then, nonadherent cells were removed by vigorous pipetting and the remaining adherent cells were harvested for analyses. We inspected the whole-genome gene expression profiles of NLCs (control sample vs. lenalidomide-treated sample) derived from 4 CLL patients by microarray. Supervised analysis identified 584 genes differentially expressed upon lenalidomide treatment, 352 up-regulated and 232 down-regulated (p<0.05). RNA was extracted with the RNeasy Plus Mini kit (Qiagen, Valencia, CA, USA). Large-scale gene expression profiling (GEP) was performed by hybridizing RNA from NLCs treated or not with lenalidomide 0.5 ÂµM for 10 days (n=4) on 4X44K Whole Human Genome Microarray (Agilent Technologies, Palo alto, CA). Genes were defined as differentially expressed between groups (NLCs CTRL vs. NLCs LENALIDOMIDE) at p<0.05 (paired t-test) and fold change Â± 1.5 by using Gene Spring GX v12.6 (Agilent) software.

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Linking genomic lesions with minimal residual disease improves prognostic stratification in children with T-cell acute lymphoblastic leukaemia

Project description:GEP class prediction in association with CI-FISH (42 candidate genes) and patient MRD stratification

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Effect of Lenalidomide on human macrophages.

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Linking genomic lesions with minimal residual disease improves prognostic stratification in children with T-cell acute lymphoblastic leukaemia

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2013-11-05 | E-GEOD-39816 | biostudies-arrayexpress

Expression data of human NK cell treated with lenalidomide

Project description:Lenalidomide, an analogue of thalidomide, is immuno-modulatory drug and has been used for many types of cancer therapy. Recently, it has been reported that lenalidomide can enhance the function of NK cell during IL-2 response. However, molecular mechanism of action of lenalidomide in NK cells is unclear still. To investigate the modification by lenalidomide on NK cells, we conducted the analysis of gene expression on NK cells.

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CC-122 versus Lenalidomide

Project description:CC-122 versus Lenalidomide

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Maturation of the thalidomystery

Project description:Gene expression profile (GEP) was analyzed from cultured bone marrow (BM) samples of patients with lenalidomide-responsive versus lenalidomide-resistant myeloma after 24 hours incubation in vitro with thalidomide (Thal) (0.8 µg/ml), lenalidomide (Len) (0.5 µg/ml) or with DMSO (control).

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