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Acute leukemias are aggressive malignancies of developmentally arrested hematopoietic progenitors. We sought here to explore the possibility that changes in hematopoietic stem/progenitor cells during development might alter the biology of leukemias arising from this tissue compartment. Using a mouse model of acute T cell leukemia, we found that leukemias generated from fetal liver (FL) and adult bone marrow (BM) differed dramatically in their leukemia stem cell activity with FL leukemias showing markedly reduced serial transplantability as compared to BM leukemias. We present evidence that this difference is due to NOTCH1-driven autocrine IGF1 signaling, which is active in FL cells but restrained in BM cells by EZH2-dependent H3K27 trimethylation. Further, we confirmed this mechanism is operative in human disease and show that enforced IGF1 signaling effectively limits leukemia stem cell activity. These findings demonstrate that resurrecting dormant fetal programs in adult cells may represent an alternate therapeutic approach in human cancer.
Pubmed ID: 30269902 RIS Download
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Non-profit plasmid repository dedicated to helping scientists around the world share high-quality plasmids. Facilitates archiving and distributing DNA-based research reagents and associated data to scientists worldwide. Repository contains over 65,000 plasmids, including special collections on CRISPR, fluorescent proteins, and ready-to-use viral preparations. There is no cost for scientists to deposit plasmids, which saves time and money associated with shipping plasmids themselves. All plasmids are fully sequenced for validation and sequencing data is openly available. We handle the appropriate Material Transfer Agreements (MTA) with institutions, facilitating open exchange and offering intellectual property and liability protection for depositing scientists. Furthermore, we curate free educational resources for the scientific community including a blog, eBooks, video protocols, and detailed molecular biology resources.
View all literature mentionsSoftware repository for R packages related to analysis and comprehension of high throughput genomic data. Uses separate set of commands for installation of packages. Software project based on R programming language that provides tools for analysis and comprehension of high throughput genomic data.
View all literature mentionsThis monoclonal targets β-Actin
View all literature mentionsThis isotype control targets not applicable
View all literature mentionsThis polyclonal targets H3K27me3
View all literature mentionsThis monoclonal targets H3K4me3
View all literature mentionsThis polyclonal targets NOTCH1
View all literature mentionsThis monoclonal targets Ly-6G Ly-6C
View all literature mentionsThis monoclonal targets CD11b
View all literature mentionsThis monoclonal targets CD34
View all literature mentionsThis monoclonal targets CD271
View all literature mentionsThis monoclonal targets NK-1.1
View all literature mentionsThis monoclonal targets CD11c
View all literature mentionsThis monoclonal targets CD11b
View all literature mentionsThis monoclonal targets CD45R (B220)
View all literature mentionsThis monoclonal targets TER-119/Erythroid cells
View all literature mentionsThis monoclonal targets Ly-6G Ly-6C
View all literature mentionsThis monoclonal targets CD8a
View all literature mentionsThis monoclonal targets CD3epsilon
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
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Mus musculus with name NOD.Cg-Prkdcscid Il2rg
Software R package of functions and classes for the analysis of oligonucleotide arrays manufactured by Affymetrix. Used to process probe level data and for exploratory oligonucleotide array analysis.
View all literature mentionsSoftware package for the analysis of gene expression microarray data, especially the use of linear models for analyzing designed experiments and the assessment of differential expression.
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View all literature mentionsA script to convert Bam alignments into a wig representation file.
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View all literature mentionsCollection of pathways and pathway annotations. The core unit of the Reactome data model is the reaction. Entities (nucleic acids, proteins, complexes and small molecules) participating in reactions form a network of biological interactions and are grouped into pathways (signaling, innate and acquired immune function, transcriptional regulation, translation, apoptosis and classical intermediary metabolism) . Provides website to navigate pathway knowledge and a suite of data analysis tools to support the pathway-based analysis of complex experimental and computational data sets.
View all literature mentionsTHIS RESOURCE IS NO LONGER IN SERVICE. Documented on September 28,2023. Software application which can analyze basic Western blot data and export them for use in spreadsheet programs. Users can create standardized or custom lab reports and can share them with colleagues. Image Studio Lite has been discontinued and replaced with Empiria Studio Software.
View all literature mentionsStatistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentionsSoftware for single-cell flow cytometry analysis. Its functions include management, display, manipulation, analysis and publication of the data stream produced by flow and mass cytometers.
View all literature mentionsCell line MOLT-4 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line HPB-ALL is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line CUTLL1 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line OP9/G-DLL1 is a Stromal cell line with a species of origin Mus musculus (Mouse)
View all literature mentionsCell line Plat-E is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
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Mus musculus with name NOD.Cg-Prkdcscid Il2rg
Mus musculus with name C57BL/6J from IMSR.
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