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GSE51402
Homo sapiens
16 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
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.
Publication Title
Interleukin-3-mediated regulation of β-catenin in myeloid transformation and acute myeloid leukemia.
Sample Metadata Fields
Specimen part, Disease, Treatment
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
GATA2 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.
Publication Title
Heritable GATA2 mutations associated with familial myelodysplastic syndrome and acute myeloid leukemia.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 2 Downloadable Samples
Illumina HiSeq 2500
Description
Retinoic-acid receptor-related orphan receptor-?t-positive (ROR?t+) innate lymphoid cells (ILCs) produce interleukin (IL)-22 and IL-17, which are critical for protective immunity against enteric pathogens. The molecular mechanism underlying the development and survival of ROR?t+ ILCs is not thoroughly understood. Here we show that Dedicator of cytokinesis 8 (DOCK8), a scaffolding protein involved in cytoskeletal rearrangement and cell migration, is essential for the protective immunity against Citrobacter rodentium. A comparative RNA sequencing-based analysis reveals an impaired induction of antimicrobial peptides in the colon of DOCK8-deficient mice, which correlates with high susceptibility to infection and a very low number of IL-22-producing ROR?t+ ILCs in their GI tract. Furthermore, DOCK8-deficient ROR?t+ ILCs are less responsive to IL-7 mediated signaling, more prone to apoptosis and produce less IL-22 due to a defect in IL-23-mediated STAT3 phosphorylation. Our studies reveal an unsuspected role of DOCK8 for the function, generation and survival of ROR?t+ ILCs. Overall design: Control and DOCK8 KO mice were infected with 2X109 CFU of Citrobacter rodentium and day 8 post infection mice were sacrificed and their colons were harvested (n=5) . Total RNA was purified from the infected colons with RNeasy mini kit (Qiagen). RNA sequencing was performed (pooled RNA sample from five mice in each group) at Genomic Core Facility Southwestern Medical Center, University of Texas.
Publication Title
DOCK8 regulates protective immunity by controlling the function and survival of RORγt+ ILCs.
Sample Metadata Fields
No sample metadata fields
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