Filters
Technology
Platform
Homo sapiens
31 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a)
Description
A "Cartes d'Identite des Tumeurs" (CIT) project from the french Ligue Nationale Contre le Cancer (<a href="http://cit.ligue-cancer.net" target="_blank">http://cit.ligue-cancer.net</a>). 104 samples; Affymetrix U133A micro-arrays.<br></br> <br></br> Ninety two patients with T-ALL were diagnosed and treated at Saint-Louis hospital, Paris. Seven patients were studied at diagnosis and relapse (total 99 T-ALL samples). There were 56 children (median age 9 years old; range 1 to 16), and 36 adults (median age 27; range 17 to 66). Informed consent was obtained from the patients and/or relatives. T-ALL diagnosis was based on morphological and immunophenotypical criteria using flow cytometry and an extended monoclonal antibody panel.<br></br> <br></br> Using a combination of molecular cytogenetic and large-scale expression analysis in human T-ALL, we identified and characterized a new recurrent chromosomal translocation, targeting the major homeobox gene cluster HOXA and the TCRB locus. Specific quantitative PCR analysis showed that the expression of the whole HOXA gene cluster was dramatically dysregulated in the HOXA-rearranged cases, and also in MLL and CALM-AF10-related T-ALL cases, strongly suggesting that HOXA genes are oncogenic in these leukemias. Inclusion of HOXA-translocated cases in a general molecular portrait of 92 T-ALL based on large-scale expression analysis shows that this rearrangement defines a new homogeneous subgroup, which shares common biological networks with the TLX1 and TLX3-related cases. Since T-ALLs derive from T-cell progenitors, expression profiles of the distinct T-ALL subgroups were analyzed with respect to those of normal human thymic sub-populations. Inappropriate utilization or perturbation of specific molecular networks involved in thymic differentiation was detected. Moreover, we found a significant association between T-ALL oncogenic subgroups and ectopic expression of a limited set of genes, including several developmental genes, namely HOXA, TLX1, TLX3, NKX3-1, SIX6 and TFAP2C. These data strongly support the view that the abnormal expression of developmental genes, including the prototypical homeobox genes HOXA, is critical in T-ALL oncogenesis.<br></br> <br></br> Project Leader: <br></br> FranC'ois Sigaux<br></br> Institut Universitaire d'Hematologie<br></br> Hopital Saint Louis, Paris, France<br></br> <br></br> Data submission:<br></br>Fabien Petel
Publication Title
HOXA genes are included in genetic and biologic networks defining human acute T-cell leukemia (T-ALL).
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Disease stage, Subject
View Samples- Homo sapiens
- 40 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
Gene signature determination of the effect of a new bromodomain inhibitor among a representative set of leukemic cell lines
Publication Title
BET inhibitor OTX015 targets BRD2 and BRD4 and decreases c-MYC in acute leukemia cells.
Sample Metadata Fields
Cell line, Compound
View Samples- 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
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
comparative expression between stromal MS5 cells treated with (MS5_PD18) or without (MS5_DMSO) MEKi
Publication Title
Interleukin-18 produced by bone marrow-derived stromal cells supports T-cell acute leukaemia progression.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 213 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Pediatric acute myeloid leukemia (AML) is a heterogeneous disease characterized by non-random genetic aberrations related to outcome. Detecting these aberrations however still lead to failures or false negative results. Therefore, we focused on the potential of gene expression profiles (GEP) to classify pediatric AML.
Publication Title
Evaluation of gene expression signatures predictive of cytogenetic and molecular subtypes of pediatric acute myeloid leukemia.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 25 Downloadable Samples
NextSeq 500
Description
We examined the brain''s choroid plexus and myeloid cell populations isolated from the brain of 5XFAD Alzheimer''s disease transgenic mice following PD-1 blockade Overall design: Choroid plexus samples and myeloid cell populations were isolated from the brain of 5XFAD mice following PD-1 blockade, and sequenced. For choroid plexus samples, 5 mice were treated with anti-PD-1, 5 with IgG control, and 4 were left untreated. For the myeloid cells samples, myeloid cells sorted from the brains of 5XFAD mice according to a gating strategy that seperate microglia (CD11b+CD45-low) and monocytes-derived macrophages (CD11b+CD45-high).
Publication Title
PD-1 immune checkpoint blockade reduces pathology and improves memory in mouse models of Alzheimer's disease.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Mus musculus
- 5 Downloadable Samples
- NextSeq 500
Description
Alzheimer's disease (AD) is a heterogeneous disorder with multiple etiologies. Harnessing the immune system by blocking the programmed cell death receptor (PD)-1 pathway in an amyloid beta mouse model was shown to evoke a sequence of immune responses that lead to disease modification. Here, blocking PD-L1, a PD-1 ligand, was found to have similar efficacy to that of PD-1 blocking in disease modification, in both animal models of AD and of tauopathy. Targeting PD-L1 in a tau-driven disease model resulted in increased immunomodulatory monocyte-derived macrophages within the brain parenchyma. Single cell RNA-seq revealed that the homing macrophages expressed unique scavenger molecules including macrophage scavenger receptor 1 (MSR1), which was shown here to be required for the effect of PD-L1 blockade in disease modification. Overall, our results demonstrate that immune checkpoint blockade targeting the PD-1/PD-L1 pathway leads to modification of common factors that go awry in AD and dementia, and thus can potentially provide an immunotherapy to help combat these diseases. Overall design: Cell populations were sorted with FACSAriaIII (BD Biosciences, San Jose, CA). Prior to sorting, all samples were filtered through a 40-µm nylon mesh. For the isolation of monocytes-derived macrophages, samples were gated for CD45high and CD11bhigh (Brilliant-violet-421, 1:150, 30-F11, Biolegend Inc. San Diego, CA; APC CD11b, 1:100, M1/70, eBioscience), while excluding doublets. Isolated cells were single cell sorted into 384-well cell capture plates containing 2?µL of lysis solution and barcoded poly(T) reverse-transcription (RT) primers for single-cell RNA-seq84. Four empty wells were designated in each 384-well plate as a no-cell control during data analysis. Immediately after sorting, each plate was spun down to ensure cell immersion into the lysis solution, snap frozen on dry ice, and stored at -80?°C until processing. Single-cell libraries were prepared as previously described73. In brief, mRNA from cells sorted into cell capture plates was barcoded, converted into cDNA, and pooled using an automated pipeline. The pooled sample was then linearly amplified by T7 in vitro transcription, and the resulting RNA was fragmented and converted into a sequencing-ready library by tagging the samples with pooled barcodes and Illumina sequences during ligation, RT, and PCR. Each pool of cells was tested for library quality, and concentration was assessed, as described73.
Publication Title
PD-1/PD-L1 checkpoint blockade harnesses monocyte-derived macrophages to combat cognitive impairment in a tauopathy mouse model.
Sample Metadata Fields
Age, Specimen part, Cell line, Treatment, Subject
View Samples
GSE77741- Homo sapiens
- 100 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
MLL rearrangements impact outcome in HOXA-deregulated T-lineage acute lymphoblastic leukemia: a Children's Oncology Group Study.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 100 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The clinical and cytogenetic features associated with T-cell acute lymphoblastic leukemia (T-ALL) are not predictive of early treatment failure or relapse. We used the Affymetrix U133 Plus 2.0 chip to profile 100 newly diagnosed patients who were treated in the Children's Oncology Group (COG) T-ALL AALL0434. We performed unsupervised hierarchical clustering of 25 HOXA probe sets within the cohort of 100 T-ALL cases. We identified a cluster of 20 cases (20%) characterized by increased expression of HOXA3, 5, 7, 9, and 10. In samples with HOXA9/10 deregulation, the presence of specific molecular lesions were confirmed through a systematic review of cytogenetic databases, FISH and PCR testing, and by RNA sequence analysis. Because MLL and AF10 genes rearrangements (MLL-R, AF10-R) are hallmarks of HOXA-deregulated leukemias, we sought to identify specific genes that are enriched with these genomic abnormalities.
Publication Title
MLL rearrangements impact outcome in HOXA-deregulated T-lineage acute lymphoblastic leukemia: a Children's Oncology Group Study.
Sample Metadata Fields
Specimen part, Disease
View Samples- Mus musculus
- 89 Downloadable Samples
- NextSeq 500
Description
Alzheimer''s disease (AD) is a detrimental neurodegenerative disease with no effective treatments. Due to cellular heterogeneity, the roles of immune cell subsets in AD onset and progression are poorly understood. By transcriptional single cell sorting, we comprehensively map all immune populations in wild type and AD–transgenic (Tg-AD) mouse brains. We describe a novel microglia type associated with neurodegenerative diseases (DAM) and identify the markers, spatial-location, and pathways associated with these cells. Immunohistochemical staining of mice and human brain slices showed DAM with intracellular/phagocytic Aß particles. Single cell analysis of DAM in Tg-AD and Trem2-/- Tg-AD revealed that the DAM program is activated in a two-step process. Activation is initiated in a Trem2 independent manner which involves down-regulation of microglia checkpoints, followed by activation of a Trem2-dependent program. These data identify a unique microglia-type, which may have important implications for future treatment of AD and other neurodegenerative diseases. Overall design: Transcriptional profiling of single cells from immune populations of mouse models of neurodegenerative diseases with matched controls, generated from deep sequencing of tens of thousands of cells, sequenced in several batches on illumina Nextseq500
Publication Title
A Unique Microglia Type Associated with Restricting Development of Alzheimer's Disease.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples