Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) is a distinct subtype of B-ALL with a poor prognosis. Rearrangement of LYN is a recurrent genetic abnormality in Ph-like ALL, but functional analysis of LYN-related fusion genes identified in ALL has not been reported. In this study, we performed functional analysis of the NCOR1-LYN fusion gene identified in a pediatric Ph-like ALL patient to establish its potential for molecular targeted therapy. Retroviral transduction of interleukin (IL)-3-dependent Ba/F3 cells with NCOR1-LYN enabled IL-3-independent proliferation, with constitutive phosphorylation of the tyrosine residues of the LYN kinase domain in the fusion protein. Replacing tyrosine residues with phenylalanine in the LYN kinase domain abolished IL-3 independence. Tyrosine kinase inhibitor dasatinib killed Ba/F3 cells expressing NCOR1-LYN in vitro accompanied by dephosphorylation of the tyrosine residues of the LYN kinase domain in the fusion protein.
Leukemic cells expressing NCOR1-LYN are sensitive to dasatinib in vivo in a patient-derived xenograft mouse model.
Cell line
View SamplesWe identified fibro-inflammatory and keratin gene expression signatures in systemic sclerosis skin.
Dissecting the heterogeneity of skin gene expression patterns in systemic sclerosis.
Age, Specimen part, Race, Subject, Time
View SamplesWe identified eighty two skin transcripts significantly correlated with the severity of interstitial lung disease (ILD) in systemic sclerosis.
Skin gene expression correlates of severity of interstitial lung disease in systemic sclerosis.
Age, Specimen part, Race, Subject
View SamplesBrassinosteroids (BRs) are growth-promoting plant hormones that play a role in abiotic stress responses, but molecular modes that enable this activity remain largely unknown. Here we show that BRs participate in the regulation of freezing tolerance. BR signaling-defective mutants of Arabidopsis thaliana were hypersensitive to freezing before and after cold acclimation. The constitutive activation of BR signaling, in contrast, enhanced freezing resistance. Evidence is provided that the BR-controlled basic helixloophelix transcription factor CESTA (CES) can contribute to the constitutive expression of the C-REPEAT/DEHYDRATION-RESPONSIVE ELEMENT BINDING FACTOR (CBF) transcriptional regulators that control cold responsive (COR) gene expression. In addition, CBF-independent classes of BR-regulated COR genes are identified that are regulated in a BR- and CES-dependent manner during cold acclimation. A model is presented in which BRs govern different cold-responsive transcriptional cascades through the posttranslational modification of CES and redundantly acting factors. This contributes to the basal resistance against freezing stress, but also to the further improvement of this resistance through cold acclimation.
Brassinosteroids participate in the control of basal and acquired freezing tolerance of plants.
Age, Specimen part, Treatment
View SamplesRNA-Seq analysis of SSA treated cells Overall design: HeLa cells, nuclear and cytoplasmic fractions, treated with SSA or MeOH
Global analysis of pre-mRNA subcellular localization following splicing inhibition by spliceostatin A.
No sample metadata fields
View SamplesIn mouse models, the bromodomain PHD finger transcription factor (BPTF) chromatin remodeling subunit in tumor cells suppresses natural killer (NK) cell antitumor activity.
BPTF Depletion Enhances T-cell-Mediated Antitumor Immunity.
Specimen part, Cell line
View SamplesDepleting the NURF chromatin remodeling complex results in enhanced antitumor immunity using mouse tumor models syngenic to two strain backgrounds.
BPTF Depletion Enhances T-cell-Mediated Antitumor Immunity.
Specimen part
View SamplesOverarching aim is to achieve a greater understanding of the control of progenitor cells within the adult human retina within the normal and diseased retinal microenvironment. Specifically we will assess via our experimental designs: (i) the control of CD133+ retinal cell populations that display mitotic potential and differentiation and
CD133+ adult human retinal cells remain undifferentiated in Leukaemia Inhibitory Factor (LIF).
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Using gene expression to predict differences in the secretome of human omental vs. subcutaneous adipose tissue.
Sex, Specimen part
View Samplesp73 is a p53 family transcription factor that plays critical roles during development and tumor suppression. We analyzed p73 activity using a combination of ChIP-on-Chip and gene expression profiling, both at baseline and after treatment with the mTOR inhibitor rapamycin.
Differential regulation of the p73 cistrome by mammalian target of rapamycin reveals transcriptional programs of mesenchymal differentiation and tumorigenesis.
Treatment
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