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GSE38519
Homo sapiens
4 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Bortezomib (Velcade) is widely used for the treatment of various human cancers, however, its mechanisms of action are not fully understood, particularly in myeloid malignancies. Bortezomib is a selective and reversible inhibitor of the proteasome. Paradoxically, we find that Bortezomib induces proteasome-independent degradation of TRAF6 protein, but not mRNA, in Myelodysplastic syndrome (MDS) and Acute Myeloid Leukemia (AML) cell lines and primary cells. The reduction in TRAF6 protein coincides with Bortezomib-induced autophagy, and subsequently with apoptosis in MDS/AML cells. RNAi-mediated knockdown of TRAF6 sensitized Bortezomib-sensitive and -resistant cell lines, underscoring the importance of TRAF6 in Bortezomib-induced cytotoxicity. Bortezomib-resistant cells expressing an shRNA targeting TRAF6 were resensitized to the cytotoxic effects of Bortezomib due to down-regulation of the proteasomal subunit alpha-1 (PSMA1). To uncover the molecular consequences following loss of TRAF6 in MDS/AML cells, we applied gene expression profiling and identified an apoptosis gene signature. Knockdown of TRAF6 in MDS/AML cell lines or patient samples resulted in rapid apoptosis and impaired malignant hematopoietic stem/progenitor function. In summary, we describe novel mechanisms by which TRAF6 is regulated through Bortezomib/autophagy-mediated degradation and by which it alters MDS/AML sensitivity to Bortezomib by controlling PSMA1 expression.
Publication Title
Cytotoxic effects of bortezomib in myelodysplastic syndrome/acute myeloid leukemia depend on autophagy-mediated lysosomal degradation of TRAF6 and repression of PSMA1.
Sample Metadata Fields
Treatment
View Samples- Saccharomyces cerevisiae
- 17 Downloadable Samples
- Affymetrix Yeast Genome S98 Array (ygs98)
Description
Diurnal temperature cycling is an intrinsic characteristic of many exposed microbial ecosystems. However, its influence on yeast physiology and transcriptome has not been studied in detail. In this study, 24-h sinoidal temperature cycles, oscillating between 12 and 30C, were imposed on anaerobic, glucose-limited chemostat cultures of Saccharomyces cerevisiae. After three diurnal temperature cycles (DTC), concentrations of glucose, and extracellular metabolites, as well as CO2-production rates showed regular, reproducible circadian rhytms. DTC also led to waves of transcriptional activation and repression, which involved one sixth of the yeast genome. A substantial fraction of these DTC-responsive genes appeared to primarily respond to changes in glucose concentration. Elimination of known glucose-responsive genes revealed overrepresentation of previously identified temperature-responsive genes as well as genes involved in cell cycle and de novo purine biosynthesis. Analyses of budding index and flow cytomery demonstrated that DTC led to a partial synchronization of the cell cycle of the yeast populations in the chemostat cultures, which was lost upon release from DTC. Comparison of DTC results with data from steady-state cultures showed that DTC was sufficiently slow to allow S. cerevisiae chemostat cultures to almost completely acclimatize their transcriptome and physiology at the DTC temperature maximum, and to approach acclimation at the DTC temperature minimum.
Publication Title
Physiological and transcriptional responses of anaerobic chemostat cultures of Saccharomyces cerevisiae subjected to diurnal temperature cycles.
Sample Metadata Fields
No sample metadata fields
View Samples- Arabidopsis thaliana
- 6 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Systemic transcriptional responses in Arabidopsis thaliana distal leaves to wounding
Publication Title
The plant NADPH oxidase RBOHD mediates rapid systemic signaling in response to diverse stimuli.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 188 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Association between gene and miRNA expression profiles and stereotyped subset #4 B-cell receptor in chronic lymphocytic leukemia.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 188 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Highly homologous B-cell receptors, stereotyped BCR, are expressed in a recurrent fraction of patients with chronic lymphocytic leukemia (CLL). In this study, we investigated the biological and molecular features of leukemic cells from 16 patients utilizing stereotyped subset #4 BCR (IGHV4-34) in a prospective cohort of 462 Binet stage A CLL patients. All subset #4 patients were characterized by the IGHV mutated gene configuration and by the absence of unfavorable cytogenetic lesions, and NOTCH1 and SF3B1 mutations. Gene expression profiling demonstrated a significant downregulation of WDFY4, MF2A and upregulation of PDGFA, FGFR1 and TFEC genes in leukemic cells from subset #4 compared to those from the remaining IGHV-mutated patients. Similarly, in the cells from subset #4 cases there was a specific miRNA expression pattern involving the upregulation of miR-497 and miR-29c. Furthermore transfection of miR-497 mimic in primary leukemic CLL cells induced a downregulation of BCL2, known to be a validated target of this miRNA. Our data identify a distinct gene and miRNA expression profile of the cells from subset #4 patients, providing further evidence for the putative role of BCR in shaping the features of the leukemic cells.
Publication Title
Association between gene and miRNA expression profiles and stereotyped subset #4 B-cell receptor in chronic lymphocytic leukemia.
Sample Metadata Fields
No sample metadata fields
View Samples- Danio rerio
- 6 Downloadable Samples
IlluminaHiSeq2500
Description
We report gene expression data for FACS sorted zebrafish mpeg1:mCherry + and mpx:EGFP + cells collected from whole embryos at 72 hours post fertilization (hpf). We also report gene expression data for the remaining, transgene negative, portion of these embryos. Overall design: ~1,000 mpeg1:mCherry+; mpx:EGFP+ transgenic embryos were homogenized, filtered, and sorted using FACS into PBS, collecting >50,000 cells for each of the three populations: mpeg1:mCherry+, mpx:EGFP+ and double negative (no double positive cells were collected as there was almost no overlap between mCherry and EGFP expression).
Publication Title
Distinct Roles for Matrix Metalloproteinases 2 and 9 in Embryonic Hematopoietic Stem Cell Emergence, Migration, and Niche Colonization.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 76 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Clinical monoclonal B lymphocytosis versus Rai 0 chronic lymphocytic leukemia: A comparison of cellular, cytogenetic, molecular, and clinical features.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 76 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Prospective series of 136 clinical monoclonal B lymphocytosis (cMBL) and 216 chronic lymphocytic leukemia (CLL) Rai 0 patients, were investigated in this study. While the distribution of CD38 and ZAP-70 positivity was similar, IGHV-mutated cases were more frequent among cMBL (P = 0.005). A Cox multivariate analysis on the whole patient cohort showed that cMBL condition was predictive of longer PFS, while CD38 expression and IGHV-unmutated status and CD38 expression correlated significantly with a shorter PFS in cMBL and Rai0-CLL, respectively. Trisomy 12, 11q- and 17p- abnormalities were scanty and of no predictive value in both conditions. Notably, gene and miRNA expression profiling showed no significant differences between cMBL and Rai0-CLL. Furthermore, similar gene and miRNA expression signatures were found in cMBL and Rai0-CLL according to the IGHV gene mutational status: that is, unmutated cases had different signatures from mutated cases, irrespectively of the cMBL or CLL condition. Overall, our study based on a prospective series of patients indicates that no major biological differences exist in cMBL compared to Rai0-CLL, suggesting that this two entities mainly differ for the initial size of the monoclonal cell population which may reflect in the longer time for clonal expansion.
Publication Title
Clinical monoclonal B lymphocytosis versus Rai 0 chronic lymphocytic leukemia: A comparison of cellular, cytogenetic, molecular, and clinical features.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 70 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st), Affymetrix Mapping 250K Nsp SNP Array (mapping250knsp)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Chromosome 2p gain in monoclonal B-cell lymphocytosis and in early stage chronic lymphocytic leukemia.
Sample Metadata Fields
Disease, Disease stage, Subject
View Samples- Homo sapiens
- 70 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st), Affymetrix Mapping 250K Nsp SNP Array (mapping250knsp)
Description
Chronic lymphocytic leukemia (CLL) is a clinically heterogeneous disease characterized by chromosomal aberrations of prognostic significance. Recent studies showed that gain of chromosome 2p is a recurrent lesion in CLL. We investigated the 2p gain and its relationship with prognostic biomarkers in a prospective series of 287 early-stage CLLs (Binet A). The 2p gain was detected by FISH in 17 patients (6%) and further characterized by single nucleotide polymorphism-array. Overall, unfavorable cytogenetic deletions, i.e. del(11)(q23) and del(17)(p13) (P=0.002) as well as unmutated (UM) status of IGHV (P<110-4) and CD38 (P<110-4) and ZAP-70 positive expression (P=0.003) were significantly more prevalent in 2p gain cases. Furthermore, 2p gained patients showed a significantly higher occurrence of stereotyped HCDR3 sequences compared to 2p normal CLLs (P=0.009). Among the stereotyped subsets, the incidence of subset #1 in 2p positive patients was significantly higher than that found in the remaining CLLs (P=0.031). Finally, gene expression profiling analysis identified a number of genes significantly upregulated in 2p gain CLLs. Among those located at 2p, NCOA1 and ROCK2 are known for their involvement in tumor progression in several human cancers, whereas among those located in different chromosomes, CAV1 at 7q31.1 has been recently identified to play a critical role in CLL progression. Our study indicates that 2p gain is a recurrent lesion in early CLL, correlated with the major biological and cytogenetic risk markers of the disease. Moreover, we provide insights to define novel candidate genes that may play additional pathogenetic roles in CLL.
Publication Title
Chromosome 2p gain in monoclonal B-cell lymphocytosis and in early stage chronic lymphocytic leukemia.
Sample Metadata Fields
Disease, Disease stage, Subject
View Samples