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A Human IPS Model I...
A Human IPS Model Implicates Embryonic B-Myeloid Fate Restriction as Developmental Susceptibility to B Acute Lymphoblastic Leukemia-Associated ETV6-RUNX1
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- Böiers, Charlotta (author)
- Lund University,Lunds universitet,Stamcellscentrum (SCC),Avdelningen för stamcellsforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Utvecklingslymfopoes och leukemi,Forskargrupper vid Lunds universitet,Stem Cell Center,Division of stem cell research,Department of Laboratory Medicine,Faculty of Medicine,Developmental lymphopoiesis and leukemia,Lund University Research Groups,UCL Cancer Institute
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- Richardson, Simon E. (author)
- UCL Cancer Institute
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- Laycock, Emma (author)
- UCL Cancer Institute
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- Zriwil, Alya (author)
- Lund University,Lunds universitet,Stamcellscentrum (SCC),Avdelningen för stamcellsforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Stem Cell Center,Division of stem cell research,Department of Laboratory Medicine,Faculty of Medicine
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- Turati, Virginia A. (author)
- UCL Cancer Institute
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- Brown, John (author)
- UCL Cancer Institute
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- Wray, Jason P. (author)
- UCL Cancer Institute
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- Wang, Dapeng (author)
- UCL Cancer Institute
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- James, Chela (author)
- UCL Cancer Institute
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- Herrero, Javier (author)
- UCL Cancer Institute,University of Edinburgh,University of Oxford
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- Sitnicka, Ewa (author)
- Karolinska Institutet,Lund University,Lunds universitet,Stamcellscentrum (SCC),Avdelningen för stamcellsforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Stem Cell Center,Division of stem cell research,Department of Laboratory Medicine,Faculty of Medicine
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- Karlsson, Stefan (author)
- Lund University,Lunds universitet,Stamcellscentrum (SCC),Avdelningen för stamcellsforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Stem Cell Center,Division of stem cell research,Department of Laboratory Medicine,Faculty of Medicine
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- Smith, Andrew J.H. (author)
- University of Edinburgh,University of Oxford
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- Jacobsen, Sten Erik W. (author)
- Karolinska Institute,Karolinska University Hospital,University of Oxford
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- Enver, Tariq (author)
- Lund University,Lunds universitet,Stamcellscentrum (SCC),Avdelningen för stamcellsforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Stem Cell Center,Division of stem cell research,Department of Laboratory Medicine,Faculty of Medicine,UCL Cancer Institute
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(creator_code:org_t)
- Elsevier BV, 2018
- 2018
- English.
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In: Developmental Cell. - : Elsevier BV. - 1534-5807 .- 1878-1551. ; 44:3, s. 7-377
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Abstract
Subject headings
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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. Böiers, Richardson et al. explore the potential for a developmental susceptibility to childhood acute lymphoblastic leukemia. Characterization of earliest B cell progenitors in human fetal liver identified a unique progenitor compartment that can be recapitulated using human pluripotent stem cells to model the impact of the pre-leukemia-initiating oncogene ETV6-RUNX1.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Keyword
- acute lymphoblastic leukemia
- B cell
- CRISPR/Cas9
- ETV6-RUNX1
- genome engineering
- human fetal lymphopoiesis
- human pluripotent stem cells
- in vitro B cell differentiation
Publication and Content Type
- art (subject category)
- ref (subject category)
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Böiers, Charlott ...
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Richardson, Simo ...
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Laycock, Emma
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Zriwil, Alya
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Turati, Virginia ...
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Brown, John
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Wray, Jason P.
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Wang, Dapeng
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James, Chela
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Herrero, Javier
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Sitnicka, Ewa
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Karlsson, Stefan
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Smith, Andrew J. ...
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Jacobsen, Sten E ...
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Enver, Tariq
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Developmental Ce ...
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Lund University
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Karolinska Institutet