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GSE37302
Homo sapiens
9 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Multiple myeloma (MM)-induced osteoclast (OC) formation occurs in close contact with MM cell infiltration into the bone marrow (BM) due to the imbalance of the receptor activator of NF-kappa-B ligand (RANKL)/osteoprotegerin (OPG) ratio in favor of RANKL in the micorenvironment. Soluble factors including CCL3/MIP-1?, IL7 and IL-3 also contribute to the increased OC formation in MM.The immunomodulatory drugs (IMiDs) directly inhibit OCs, however their effect on the mechanisms involved in MM-induced OC formation are not known and have been investigated in this study. We found that both Lenalidomide (LEN) and Pomalidomide (POM), at concentration ranging reached in vivo, significantly blunted RANKL up-regulation normalizing the RANKL/OPG ratio in human BM osteoprogenitor cells (PreOBs) co-cultured with MM cells and inhibited CCL3/MIP-1? production by MM cells. The reduction of CD49d expression on MM cells, a molecule critically involved in RANKL up-regulation in the micorenvironment, accompanied this effect. Consistently the pro-osteoclastogenic property of the conditioned medium of MM cells co-cultured with PreOBs was reduced in the presence of both IMiDs. By microarray analysis we further investigated the effect of POM and LEN on the transcriptional profile of both MM cells and PreOBs. We found a significant down-regulation in MM cells, in addition to CD49d, of genes belonging to the adhesion molecules family such as ITGA8 and ICAM2 (CD102) induced by both IMiDs compounds. In conclusion our data suggest that POM and LEN inhibits MM-induced OC formation through the inhibition of RANKL/OPG ratio targeting the expression of adhesion molecules by MM cells.
Publication Title
Immunomodulatory drugs lenalidomide and pomalidomide inhibit multiple myeloma-induced osteoclast formation and the RANKL/OPG ratio in the myeloma microenvironment targeting the expression of adhesion molecules.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Myeloma bone disease is characterized by tremendous bone destruction with suppressed bone formation. IL-3 is a multifunctional cytokine that increases myeloma cell growth and osteoclast proliferation while inhibiting osteoblast differentiation. While IL-3 appears to be an attractive therapeutic target for myeloma, attempts at targeting IL-3 have been unsuccessful due to IL-3s effects on normal hematopoiesis. Thus identification of IL-3s downstream effects in MMBD is important for effective targeting of this cytokine in MM. Here we demonstrated that treatment of myeloma patient CD14+ bone marrow monocyte / macrophages with IL-3 induces high levels of Activin A (ActA), a pluripotent TGF- superfamily member that, like IL-3, modulates MMBD by enhancing osteoclastogenesis and inhibiting osteoblasts. We show that IL-3 induced osteoclastogenesis is mediated by ActA and is RANKL independent. Additionally, IL-3 induced ActA secretion is greatest early in osteoclastogenesis and ActA acts early in osteoclastogenesis. Therefore we suggest that therapies targeting ActA production should block IL-3s effects in myeloma bone disease.
Publication Title
Bone marrow monocyte-/macrophage-derived activin A mediates the osteoclastogenic effect of IL-3 in multiple myeloma.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
Illumina HiSeq 2000
Description
The hematological malignancies classified as Mixed Lineage leukemias (MLL) harbor fusions of the MLL1 gene to partners that are members of transcriptional elongation complexes. MLL-rearranged leukemias are associated with extremely poor prognosis and response to conventional therapies and efforts to identify molecular targets are urgently needed. Using mouse models of MLL-rearranged acute myeloid leukemia (AML), here we show that genetic inactivation or small molecule inhibition of the protein arginine methyltransferase PRMT5 exhibit anti-tumoral activity in MLL-fusion protein driven transformation. Genome wide transcriptional analysis revealed that inhibition of PRMT5 methyltransferase activity overrides the differentiation block in leukemia cells without affecting the expression of MLL-fusion direct oncogenic targets. Furthermore, we find that this differentiation block is mediated by transcriptional silencing of the cyclin-dependent kinase inhibitor p21 (CDKN1a) gene in leukemia cells. Our study provides pre-clinical rationale for targeting PRMT5 using small molecule inhibitors in the treatment of leukemias harboring MLL-rearrangements. Overall design: RNA-seq data from 72h-treated DMSO and EPZ 015666 (PRMT5i) MLL-ENL/NrasG12D leukemia cells, three independent replicates.
Publication Title
Genetic deletion or small-molecule inhibition of the arginine methyltransferase PRMT5 exhibit anti-tumoral activity in mouse models of MLL-rearranged AML.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Homo sapiens
- 66 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Gastric cancers with mismatch repair (MMR) inactivation are characterised by microsatellite instability (MSI). In this study, the transcriptional profile of 38 gastric cancers with and without MSI was analysed.
Publication Title
Genome-wide expression profile of sporadic gastric cancers with microsatellite instability.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The involvement of osteocytes in multiple myeloma (MM)-induced osteoclast formation and the occurrence of bone lesions are still unknown. Osteocytes regulate bone remodeling at least in part through the cell death and apoptosis triggering osteoclast recruitment and formation. In this study, firstly we shown that MM cells increased osteocyte death and affect their transcriptional profile evaluated by microarray analysis up-regulating osteoclastogenic cytokines as interleukin (IL)-11. Consistently we show that the conditioned media of human pre-osteocytes co-cultured with MM cells significantly increased osteoclastogenesis. To translate into a clinical perspective such in vitro evidences, we then performed histological analysis on bone biopsies obtained from MM patients, MGUS and healthy controls. We found a significant reduction in the number of viable osteocytes in MM patients as compared to controls. A significant negative correlation between the number of viable osteocytes and that of osteoclasts was also demonstrated. Moreover, as regards the skeletal involvement, we found that MM patients with bone lesions have a significant lower number of viable osteocyte than those without. Overall, our data suggest a role of osteocytic cell death in MM-induced osteoclast formation in vitro and MM bone disease in vivo in MM patients.
Publication Title
Increased osteocyte death in multiple myeloma patients: role in myeloma-induced osteoclast formation.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 27 Downloadable Samples
- Illumina HiSeq 2000
Description
Multiple myeloma (MM) is a malignant proliferation of bone marrow plasma cells (PCs) characterized by highly heterogeneous genetic background and clinical course, and whose pathogenesis remains largely unknown. Long ncRNAs (lncRNAs) are a large class of non-protein-coding RNA, involved in many physiological cellular and genomic processes as well as in carcinogenesis, cancer metastasis and invasion. Although still in its infancy, the knowledge of the role of lncRNAs in MM is progressively expanding. Besides studies on selected candidates, lncRNAs expression at genome-wide transcriptome level is confined to microarray technologies, thus investigating a limited collection of transcripts. Herein, we assessed the lncRNAs expression profiling by RNA-sequencing in a cohort of 30 MM patients, aimed at defining a comprehensive catalogue of lncRNAs specifically associated with the main MM molecular subgroups and genetic alterations. We identified 391 deregulated lncRNAs, 67% of which were also detectable and validated by whole-transcript microarrays. In addition, we identified a list of lncRNAs, with potential relevance in MM, co-expressed and in close proximity to genes that might undergo a cis-regulatory relationship. Overall design: Total RNA samples from highly purified plasma cells of 30 MM cases at onset
Publication Title
Expression Pattern and Biological Significance of the lncRNA ST3GAL6-AS1 in Multiple Myeloma.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Subject
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Gene expression profiles of 8 samples of CD34+derived normal promyelocytes
Publication Title
Identification of a molecular signature for leukemic promyelocytes and their normal counterparts: Focus on DNA repair genes.
Sample Metadata Fields
Specimen part
View Samples- Triticum turgidum subsp. durum, Triticum aestivum
- 17 Downloadable Samples
- Affymetrix Wheat Genome Array (wheat)
Description
To provide a global study of transcriptome changes under drought stress, the gene expression levels of a durum wheat genotype (Triticum durum Desf. cultivar Creso) and two bread wheat genotypes (Triticum aestivum L. cultivar Chinese Spring -CS- and its deletion line CS_5AL-10) were investigated. The 5A chromosome deletion line (5AL-10) lacks the distal part (43%) of the long arm of chromosome 5A. Each genotype was subjected to two different levels of water stress at the grain filling stage. After anthesis, three different levels of soil water content (SWC) were induced as described below: control (CTRL; SWC=28%), moderate stress (MS; SWC=18%), and severe stress (SS; SWC=12.5%). For each sample, three biological replicates were performed, for a total of 27 hybridizations. ****[PLEXdb(http://www.plexdb.org) has submitted this series at GEO on behalf of the original contributor, Alessio Aprile. The equivalent experiment is TA23 at PLEXdb.]
Publication Title
Transcriptional profiling in response to terminal drought stress reveals differential responses along the wheat genome.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
A rare complication of multiple myeloma is a secondary extramedullary involvement, and the skin is one of the possible sites, due to the physiological homing of plasma cells (PCs) into the skin. The article reports a case of a relapsed refractory MM patient, who developed a cutaneous localization after 16 months from the diagnosis under Bortezomib treatment without a leukemic phase. Patient was refractory to Bortezomib. We analyzed the gene expression profiles, the immunophenotypic and immunohistochemistry profiles of MM cells across the course of the disease at the bone marrow and skin localization. Data obtained were further expanded by an immunohistochemistry analysis on selected molecules in a large cohort of MM patients with cutaneous localization. In particular we focused on the expression of chemokines and chemokine receptors involved in the PC skin homing.
Publication Title
Cutaneous localization in multiple myeloma in the context of bortezomib-based treatment: how do myeloma cells escape from the bone marrow to the skin?
Sample Metadata Fields
Sex, Age, Specimen part, Subject, Time
View Samples- Homo sapiens
- 33 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Molecular Aging of Human Liver: An Epigenetic/Transcriptomic Signature.
Sample Metadata Fields
Sex, Age, Specimen part, Disease
View Samples