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ETV6-RUNX1 is associated with childhood acute B-lymphoblastic leukemia (cALL) functioning as a first-hit mutation that initiates a clinically silent pre-leukemia in utero. Because lineage commitment hierarchies differ between embryo and adult, and the impact of oncogenes is cell-context dependent, we hypothesized that the childhood affiliation of ETV6-RUNX1 cALL reflects its origins in a progenitor unique to embryonic life. We characterize the first emerging B cells in first-trimester human embryos, identifying a developmentally restricted CD19-IL-7R+ progenitor compartment, which transitions from a myeloid to lymphoid program during ontogeny. This developmental series is recapitulated in differentiating human pluripotent stem cells (hPSCs), thereby providing a model for the initiation of cALL. Genome-engineered hPSCs expressing ETV6-RUNX1 from the endogenous ETV6 locus show expansion of the CD19-IL-7R+ compartment, show a partial block in B lineage commitment, and produce proB cells with aberrant myeloid gene expression signatures and potential: features (collectively) consistent with a pre-leukemic state.
Pubmed ID: 29290585 RIS Download
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Collection of human embryonic and fetal material (Tissue and RNA) ranging from 3 to 20 weeks of development available to the international scientific community. Material can either be sent to registered users or our In House Gene Expression Service (IHGES) can carry out projects on user''''s behalf, providing high quality images and interpretation of gene expression patterns. Gene expression data emerging from HDBR material is added to our gene expression database which is accessible via our HUDSEN (Human Developmental Studies Network) website. A significant proportion of the material has been cytogenetically karyotyped, and normal karyotyped material is provided for research.
View all literature mentionsAn Antibody supplier and subset of ThermoFisher Scientific which provides fluorescence reagents for various experiments and methods.
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