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accession-icon SRP070849
Combination targeted therapy to disrupt aberrant oncogenic signaling and reverse epigenetic dysfunction in IDH2- and TET2-mutant acute myeloid leukemia (RNA-Seq)
  • organism-icon Mus musculus
  • sample-icon 19 Downloadable Samples
  • Technology Badge IconIllumina HiSeq 2000

Description

Genomic studies in acute myeloid leukemias (AML) have identified mutations which drive altered DNA methylation, including TET2 and IDH. Functional studies have shown these mutations contribute to transformation, although how these mutations impact the response to epigenetic therapies is not fully delineated. Here we show AMLs with TET2/IDH2 mutations combined with FLT3ITD mutations are specifically sensitive to 5-Azacytidine or to the IDH2 inhibitor AG-221, respectively. 5-Azacytidine/AG-221 therapies induced a reduction in leukemic blasts and in stem/progenitor expansion, with attenuation of aberrant DNA hypermethylation. These therapeutic benefits were achieved through restoration of differentiation, such that normalized hematopoiesis was derived from mutant cells. Consistent with these data, at the time of clinical response to 5-Azacytidine or AG-221, most patients had mutant-derived hematopoiesis. By contrast, combined AG-221/5-Azacytidine plus FLT3 inhibition reduced disease burden and reversed epigenetic dysfunction. Our studies suggest combined targeting of signaling and epigenetic pathways can increase therapeutic response in AML. Overall design: We profiled genome-wide transcription patterns of the hematopoietic stem cells (LSK) population in Wild-type, Idh2 R140Q Flt3-ITD, and Tet2-/-;Flt3-IDT mice. Idh2 R140Q Flt3-ITD mice with AML were treated with either vehicle or AG-221 (the first small molecule in vivo inhibitor of IDH2 to enter clinical trials). Tet2-/-;Flt3-IDT mice with AML were treated with vehicle or 5-Azacytidine (Decitabine, hypomethylating agent).

Publication Title

Combination Targeted Therapy to Disrupt Aberrant Oncogenic Signaling and Reverse Epigenetic Dysfunction in <i>IDH2</i>- and <i>TET2</i>-Mutant Acute Myeloid Leukemia.

Sample Metadata Fields

Specimen part, Treatment, Subject

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accession-icon GSE16040
S. pombe genome-wide nucleosome mapping reveals positioning mechanisms distinct from S. cerevisiae
  • organism-icon Schizosaccharomyces pombe
  • sample-icon 5 Downloadable Samples
  • Technology Badge Icon Affymetrix Yeast Genome 2.0 Array (yeast2)

Description

Positioned nucleosomes limit the access of proteins to DNA and implement regulatory features encoded in eukaryotic genomes. Here we generated the first genome-wide nucleosome positioning map for Schizosaccharomyces pombe and annotated transcription start and termination sites genome-wide. Using this resource we found surprising differences compared to the nucleosome organization in the distantly related yeast Saccharomyces cerevisiae [the cerevisiae data has been published by others (PMID: 17873876) and the raw data is deposited at ArrayExpress(E-MEXP-1172)]. DNA sequence guides nucleosome positioning differently, e.g., poly(dA:dT) elements are not enriched in S. pombe nucleosome-depleted regions (NDRs). Regular nucleosomal arrays emanate more asymmetrically, i.e., mainly co-directionally with transcription, from promoter NDRs, but promoters harbouring the histone variant H2A.Z show regular arrays also upstream. Regular nucleosome phasing in S. pombe has a very short repeat length of 154 base pairs, and requires a remodeler, Mit1, conserved in humans but not found in S. cerevisiae. Nucleosome positioning mechanisms are evidently not universal but evolutionarily plastic.

Publication Title

Schizosaccharomyces pombe genome-wide nucleosome mapping reveals positioning mechanisms distinct from those of Saccharomyces cerevisiae.

Sample Metadata Fields

No sample metadata fields

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accession-icon GSE141873
Establishment and Characterisation by Expression Microarray of Patient Derived Xenograft Panel of Human Pancreatic Adenocarcinoma Patients
  • organism-icon Homo sapiens
  • sample-icon 21 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Gene 2.0 ST Array (hugene20st)

Description

mRNA expression profiling of pancreatic cancer, comparing adjacent normal tissue, patient tumour and first generation patient derived xenograft tumours

Publication Title

Establishment and Characterisation by Expression Microarray of Patient-Derived Xenograft Panel of Human Pancreatic Adenocarcinoma Patients.

Sample Metadata Fields

Specimen part

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accession-icon GSE57002
Mutant IDH inhibits HNF4a to disrupt hepatocyte differentiation and promote cholangiocarcinoma.
  • organism-icon Mus musculus
  • sample-icon 14 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)

Description

Gene expression of mouse hepatoblasts (HBs) expressing IDH1 WT, IDH1 R132C, IDH2 WT, R172K and empty vector controls (N=2 cultures for each condition) grown on collagen-coated plates and IDH1 R132C and empty vector controls on uncoated plates were evaluated using Affymetrix Mouse 430Av2 DNA microarrays that were processed at the Dana-Farber Cancer Institute core facility (http://macf-web.dfci.harvard.edu/) using their standard protocol.

Publication Title

Mutant IDH inhibits HNF-4α to block hepatocyte differentiation and promote biliary cancer.

Sample Metadata Fields

Specimen part

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accession-icon GSE80447
Expression data from proliferating and senescent IMR90 cells
  • organism-icon Homo sapiens
  • sample-icon 4 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Gene 1.0 ST Array (hugene10st)

Description

Total RNA was isolated from proliferating and senescent IMR90 cells to compare gene-expression to the changes in nucleolus-association in proliferating and senescent IMR90 cells.

Publication Title

Nucleolus association of chromosomal domains is largely maintained in cellular senescence despite massive nuclear reorganisation.

Sample Metadata Fields

Specimen part

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accession-icon GSE16495
Expression data from poplar apices
  • organism-icon Populus tremula x populus alba
  • sample-icon 4 Downloadable Samples
  • Technology Badge Icon Affymetrix Poplar Genome Array (poplar)

Description

We studied differences in gene expression between Populus P35S::EBB1 lines and control, affecting plant growth and differentiation, and dormancy. We used microarrays to detail the global program of gene expression underlying morphological and developmental changes driven by overexpression of the EBB1 gene.

Publication Title

EARLY BUD-BREAK 1 (EBB1) is a regulator of release from seasonal dormancy in poplar trees.

Sample Metadata Fields

Specimen part

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accession-icon GSE55813
Expression data from amiEBBB1 poplar apices
  • organism-icon Populus tremula x populus alba
  • sample-icon 2 Downloadable Samples
  • Technology Badge Icon Affymetrix Poplar Genome Array (poplar)

Description

We study gene expression Populus amiEBB1 lines affecting dormancy. We used microarrays to detail the global program of gene expression underlying morphological and developmental changes droved by expression of artifical micro RNA (ami) targeting EBB1 gene.

Publication Title

EARLY BUD-BREAK 1 (EBB1) is a regulator of release from seasonal dormancy in poplar trees.

Sample Metadata Fields

Specimen part

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accession-icon GSE16870
HeLa cells treated with V-ATPase inhibitors or with desoxyferramine compared to HeLa in DMSO or medium with low LDL
  • organism-icon Homo sapiens
  • sample-icon 31 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

Expression data from HeLa cells treated with V-ATPase inhibitors or with desoxyferramine compared to HeLa treated with DMSO or medium with low LDL

Publication Title

Inhibition of iron uptake is responsible for differential sensitivity to V-ATPase inhibitors in several cancer cell lines.

Sample Metadata Fields

Cell line

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accession-icon GSE15689
A complementary role for ELF3 and TFL1 in the regulation of flowering time by ambient temperature.
  • organism-icon Arabidopsis thaliana
  • sample-icon 18 Downloadable Samples
  • Technology Badge Icon Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)

Description

Plants regulate their time to flowering by gathering information from the environment. Photoperiod and temperature are among the most important environmental variables. Suboptimal, but not near-freezing, temperatures regulate flowering through the thermosensory pathway, which overlaps with the autonomous pathway. Here we show that ambient temperature regulates flowering by two genetically distinguishable pathways, one that requires TFL1 and another that requires ELF3. The delay in flowering time observed at lower temperatures was partially suppressed in single elf3 and tfl1 mutants, whereas double elf3 tfl1 mutants were insensitive to temperature. tfl1 mutations abolished the temperature response in cryptochrome mutants that are deficient in photoperiod perception, but not in phyB mutants that have a constitutive photoperiodic response. Contrary to tfl1, elf3 mutations were able to suppress the temperature response in phyB mutants, but not in cryptochrome mutants. The gene expression profile revealed that the tfl1 and elf3 effects are due to the activation of different sets of genes and identified CCA1 and SOC1/AGL20 as being important cross talk points. Finally, genome-wide gene expression analysis strongly suggests a general and complementary role for ELF3 and TFL1 in temperature signalling.

Publication Title

A complementary role for ELF3 and TFL1 in the regulation of flowering time by ambient temperature.

Sample Metadata Fields

No sample metadata fields

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accession-icon GSE12152
Genome scale transcriptome analysis of shoot organogenesis in poplar
  • organism-icon Populus tremula x populus alba
  • sample-icon 10 Downloadable Samples
  • Technology Badge Icon Affymetrix Poplar Genome Array (poplar)

Description

Regeneration of transgenic cells remains a major obstacle to research and commercial deployment of transgenic plants for most species.

Publication Title

Genome scale transcriptome analysis of shoot organogenesis in Populus.

Sample Metadata Fields

Sex

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refine.bio is a repository of uniformly processed and normalized, ready-to-use transcriptome data from publicly available sources. refine.bio is a project of the Childhood Cancer Data Lab (CCDL)

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Cite refine.bio

Casey S. Greene, Dongbo Hu, Richard W. W. Jones, Stephanie Liu, David S. Mejia, Rob Patro, Stephen R. Piccolo, Ariel Rodriguez Romero, Hirak Sarkar, Candace L. Savonen, Jaclyn N. Taroni, William E. Vauclain, Deepashree Venkatesh Prasad, Kurt G. Wheeler. refine.bio: a resource of uniformly processed publicly available gene expression datasets.
URL: https://www.refine.bio

Note that the contributor list is in alphabetical order as we prepare a manuscript for submission.

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