Filters
Technology
Platform
Homo sapiens
80 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a)
Description
Individuals with Down syndrome (DS) are predisposed to develop acute megakaryoblastic leukemia (AMKL), characterized by expression of truncated GATA1 transcription factor protein (GATA1s) due to somatic mutation. The treatment outcome for DS-AMKL is more favorable than for AMKL in non-DS patients. To gain insight into gene expression differences in AMKL, we compared 24 DS and 39 non-DS AMKL samples. We found that non-DS-AMKL samples cluster in two groups, characterized by differences in expression of HOX/TALE family members. Both of these groups are distinct from DS-AMKL, independent of chromosome 21 gene expression. To explore alterations of the GATA1 transcriptome, we used cross-species comparison with genes regulated by GATA1 expression in murine erythroid precursors. Genes repressed after GATA1 induction in the murine system, most notably GATA-2, MYC, and KIT, show increased expression in DS-AMKL, suggesting that GATA1s fail to repress this class of genes. Only a subset of genes that are up-regulated upon GATA1 induction in the murine system show increased expression in DS-AMKL, including GATA1 and BACH1, a probable negative regulator of megakaryocytic differentiation located on chromosome 21. Surprisingly, expression of the chromosome 21 gene RUNX1, a known regulator of megakaryopoiesis, was not elevated in DS-AMKL. Our results identify relevant signatures for distinct AMKL entities and provide insight into gene expression changes associated with these related leukemias.
Publication Title
Identification of distinct molecular phenotypes in acute megakaryoblastic leukemia by gene expression profiling.
Sample Metadata Fields
Sex, Age
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Myeloproliferative neoplasms are frequently associated with aberrant constitutive tyrosine kinase (TK) activity resulting from point mutations or chimaeric fusion genes, such as BCR ABL1 or JAK2 V617F. We report here for the first time in hematological malignancies, two novel fusion genes involving the TK RET, BCR-RET and FGFR1OP-RET, in chronic myelo monocytic leukemia (CMML) cases. The two RET fusion genes lead to the aberrant activation of RET, are able to transform hematopoietic cells and skew the hematopoietic differentiation program towards the monocytic/macrophage lineage. We also report that the BCR-RET fusion protein is insensitive to Imatinib but sensitive to Sorafenib in vivo. CMML is an hematopoietic malignancy associated with the frequent activation of the RAS pathway. The RET fusion genes seems to constitutively mimic the same signaling pathway than RAS mutations. Overall, the RET fusion genes behaviors in the monocytic lineage underlie the role of the normal RET TK activity during the physiological monocytic differentiation.
Publication Title
RET fusion genes are associated with chronic myelomonocytic leukemia and enhance monocytic differentiation.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 53 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Transgenic expression of TLX1 induces T-cell leukemias in mice.
Publication Title
The TLX1 oncogene drives aneuploidy in T cell transformation.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 60 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This study provides a comprehensive evaluation of changes in gene expression during treatment with Genistein in vitro.
Publication Title
Dose- and Time-Dependent Transcriptional Response of Ishikawa Cells Exposed to Genistein.
Sample Metadata Fields
Treatment
View Samples- Homo sapiens
- 72 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We have determined the gene expression profile induced by 17 alpha-ethynyl estradiol (EE) in Ishikawa cells, a human uterine-derived estrogen-sensitive cell line, at various doses (1 pM, 100 pM, 10 nM, and 1 microM) and time points (8, 24, and 48 h). The transcript profiles were compared between treatment groups and controls (vehicle-treated) using high-density oligonucleotide arrays to determine the expression level of approximately 38,500 human genes. By trend analysis, we determined that the expression of 2560 genes was modified by exposure to EE in a dose- and time-dependent manner (p </= 0.0001). The annotation available for the genes affected indicates that EE exposure results in changes in multiple molecular pathways affecting various biological processes, particularly associated with development, morphogenesis, organogenesis, cell proliferation, cell organization, and biogenesis. All of these processes are also affected by estrogen exposure in the uterus of the rat. Comparison of the response to EE in both the rat uterus and the Ishikawa cells showed that 71 genes are regulated in a similar manner in vivo as well as in vitro. Further, some of the genes that show a robust response to estrogen exposure in Ishikawa cells are well known to be estrogen responsive, in various in vivo studies, such as PGR, MMP7, IGFBP3, IGFBP5, SOX4, MYC, EGR1, FOS, CKB, and CCND2, among others. These results indicate that transcript profiling can serve as a viable tool to select reliable in vitro systems to evaluate potential estrogenic activities of target chemicals and to identify genes that are relevant for the estrogen response.
Publication Title
The genomic response of a human uterine endometrial adenocarcinoma cell line to 17alpha-ethynyl estradiol.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 70 Downloadable Samples
- Affymetrix Rat Expression 230A Array (rae230a)
Description
The rat uterus responds to acute estrogen treatment with a series of well characterized physiological responses; however, the gene expression changes required to elicit these responses have not been fully characterized. In order to understand early events induced by estrogen exposure in vivo, we evaluated the temporal gene expression in the uterus of the immature rat after a single dose of 17 Alpha-ethynyl estradiol (EE) by microarray analysis, evaluating the expression of 15,923 genes. Immature 20 day old rats were exposed to a single dose of EE (10 ug/kg) and the effect on uterine histology, weight and gene expression were determined after 1, 2, 8, 24, 48, 72 and 96 h. EE induced changes in the expression of 3,867 genes, at least at one time point (p¡Ü0.0001), and at least 1.5 fold (up- or down-regulated). Specifically, the expression of 8, 116, 3030, 2076, 381, 445, and 125 genes was modified at 1, 2, 8, 24, 48, 72 or 96 hours after exposure to EE respectively (p¡Ü0.0001, t Test). At the tissue and organ level, a clear uterotrophic response was elicited by EE after only 8 h, reaching a maximum after 24 h and remaining detectable even after 96 h of exposure. The uterine phenotypic changes were induced by sequential changes in the transcriptional status of a large number of genes, in a program that involves multiple molecular pathways. Using the gene ontology to better understand the temporal response to estrogen exposure, we determined that the earliest changes were in the expression of genes whose products are involved in transcriptional regulation and signal transduction, followed by genes implicated in protein synthesis, energy utilization, solute transport, cell proliferation and differentiation, tissue remodeling and immunological responses among other pathways. The compendium of genes here presented represents a comprehensive compilation of estrogen-responsive genes involved in the uterotrophic response.
Publication Title
Uterine temporal response to acute exposure to 17alpha-ethinyl estradiol in the immature rat.
Sample Metadata Fields
Sex, Age, Specimen part, Compound, Time
View Samples- Homo sapiens
- 57 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This study provides a comprehensive evaluation of changes in gene expression during treatment with Bisphenol A in vitro.
Publication Title
The genomic response of Ishikawa cells to bisphenol A exposure is dose- and time-dependent.
Sample Metadata Fields
Cell line, Treatment
View Samples
GSE40348- Rattus norvegicus
- 300 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
A novel transcriptomics based in vitro method to compare and predict hepatotoxicity based on mode of action.
Sample Metadata Fields
Sex, Time
View Samples- Rattus norvegicus
- 30 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
This study provides an evaluation of changes in gene expression associated with dioctyl phthalate treatment of rat hepatocytes in vitro.
Publication Title
A novel transcriptomics based in vitro method to compare and predict hepatotoxicity based on mode of action.
Sample Metadata Fields
Sex, Time
View Samples- Rattus norvegicus
- 30 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
This study provides an evaluation of changes in gene expression associated with acetominophen treatment of rat hepatocytes in vitro.
Publication Title
A novel transcriptomics based in vitro method to compare and predict hepatotoxicity based on mode of action.
Sample Metadata Fields
Sex, Time
View Samples