Aberrant activation of -catenin is a common event in Acute Myeloid Leukemia (AML), and is recognized as an independent predictor of poor prognosis. Although increased -catenin signaling in AML has been associated with AML1-ETO and PML-RAR translocation products, and activating mutations in the FLT3 receptor, it remains unclear which mechanisms activate -catenin in AML more broadly. Here, we describe a novel link between interleukin-3 (IL-3) signaling and the regulation of -catenin in myeloid transformation and AML. Using a murine model of HoxB8 and IL-3 cooperation we show that IL-3 modulates -catenin protein levels, and Cre-induced deletion of -catenin abolishes IL-3 dependent growth and colony formation. In the erythroleukemic cell line TF-1.8, we observed increased -catenin protein levels and nuclear localization in response to IL-3, which correlated with transcriptional induction of -catenin target genes. Furthermore, IL-3 promoted -catenin accumulation in a subset of AML patient samples, and microarray gene expression analysis of these cells revealed induction of WNT/-catenin and TCF4 transcriptional gene signatures in an IL-3 dependent manner. This study is the first to link -catenin activation to IL-3 and suggests that targeting IL-3 signaling may be an effective approach for the inhibition of -catenin activity in some patients with AML.
Interleukin-3-mediated regulation of β-catenin in myeloid transformation and acute myeloid leukemia.
Specimen part, Disease, Treatment
View SamplesGATA2 mutants were discovered in families predisposed to MDS/AML and in sporadic cases of CML-blast crisis. Promyelocytic HL-60 cells were transduced with lentiviral vectors that express GATA2 WT or T354M, 355delT or L359V mutants upon addition of 4-hydroxy tamoxifen (4HT). Microarrays were performed to identify GATA2 WT signatures and differences caused by these mutations.
Heritable GATA2 mutations associated with familial myelodysplastic syndrome and acute myeloid leukemia.
Specimen part, Cell line
View SamplesCutaneous, acral and mucosal subtypes of melanoma were evaluated by whole-genome sequencing, revealing genes affected by novel recurrent mutations to the promoter (TERT, DPH3, OXNAD1, RPL13A, RALY, RPL18A, AP2A1), 5-UTR (HNRNPUL1, CCDC77, PES1), and 3-UTR (DYNAP, CHIT1, FUT9, CCDC141, CDH9, PTPRT) regions. TERT promoter mutations had the highest frequency of any mutation, but neither they nor ATRX mutations, associated with the alternative telomere lengthening mechanism, were correlated with greater telomere length. Genomic landscapes largely reflected ultraviolet radiation mutagenesis in cutaneous melanoma and provided novel insights into melanoma pathogenesis. In contrast, acral and mucosal melanomas exhibited predominantly structural changes, and mutation signatures of unknown aetiology not previously identified in melanoma. The majority of melanomas had potentially actionable mutations, most of which were in components of the mitogen-activated protein kinase and phosphoinositol kinase pathways.
Whole-genome landscapes of major melanoma subtypes.
No sample metadata fields
View SamplesSkeletal muscle actin mice (Crawford et al., (2002) Mol Cell Biol 22, 5587) were crossed with cardiac actin transgenic mice (termed "ACTC^Coco" or "Coco" for short), to produce mice that had cardiac actin instead of skeletal muscle actin in their skeletal muscles (termed "ACTC^Co/KO" or for short "Coco/KO"). Microarray analysis using the Illumina mouse-6 v1.1 expression beadchip was performed on RNA extraced from the soleus muscle of Coco/KO mice and wildtype mice, to confirm the swith in actin isoform expression, and to determine what other differences might exist between wildtype mice and the Coco/KO mice.
Rescue of skeletal muscle alpha-actin-null mice by cardiac (fetal) alpha-actin.
No sample metadata fields
View SamplesThe mouse anterior-posterior (A-P) axis polarization is preceded by formation of the distal visceral endoderm (DVE). However, the mechanism of the emergence of DVE cells is not well understood. Here, we show by in vitro culturing of embryos immediately after implantation in micro-fabricated cavities (narrow; 90 micro-meter, wide; 180 miro-meter in diameter) that the external mechanical cues exerted on the embryo, i.e. cultured in the narrow cavity, are crucial for DVE formation as well as elongated egg cylinder shape. This implies that these developmental events immediately after implantation are not simply embryo-autonomous processes but require extrinsic mechanical factors. Further whole genome-wide gene expression profiles with DNA microarray revealed that no significant difference of transcripts were evident with or without mechanical cues except DVE-related markers. Thus, we propose that external mechanical cues rather than not specific molecular pathways can trigger the establishment of the A-P axis polarization, which is one of the fundamental proccesses of mammalian embryogenesis.
External mechanical cues trigger the establishment of the anterior-posterior axis in early mouse embryos.
Specimen part, Treatment
View SamplesThis study aimed to investigate the role of ß-estradiol in MCF-7 breast cancer (BC) mechanism.
No associated publication
Sex, Specimen part, Cell line
View SamplesThe bromodomain inhibitor JQ1 and the histone deacetylase inhibitor panobinostat induce synergistic anticancer effects
No associated publication
Cell line, Treatment
View SamplesAnalysis of patient-derived xenograft cells at the basal level. A panel of T- and BCP-ALL pediatric leukaemia xenograft cells were utilised to further understand the biology of pediatric leukaemia.
No associated publication
Specimen part, Disease
View SamplesThis SuperSeries is composed of the SubSeries listed below.
No associated publication
Specimen part, Cell line
View SamplesN-Myc oncoprotein induces neuroblastoma by modulating gene transcription, and long noncoding RNAs exert biological effects by regulating gene expression.
No associated publication
Specimen part
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