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Hematopoietic Stem ...
Hematopoietic Stem Cell Expansion Precedes the Generation of Committed Myeloid Leukemia-initiating Cells in C/EBP alpha Mutant AML
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Bereshchenko, Oxana (author)
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Mancini, Elena (author)
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Moore, Susan (author)
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Bilbao, Daniel (author)
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- Månsson, Robert (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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Luc, Sidinh (author)
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Grover, Amit (author)
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- Jacobsen, Sten Eirik W (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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- Bryder, David (author)
- Lund University,Lunds universitet,Institutionen för laboratoriemedicin,Medicinska fakulteten,Department of Laboratory Medicine,Faculty of Medicine
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Nerlov, Claus (author)
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(creator_code:org_t)
- Elsevier BV, 2009
- 2009
- English.
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In: Cancer Cell. - : Elsevier BV. - 1878-3686 .- 1535-6108. ; 16:5, s. 390-400
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http://dx.doi.org/10...
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Abstract
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- We here use knockin mutagenesis in the mouse to model the spectrum of acquired CEBPA mutations in human acute myeloid leukemia. We find that C-terminal C/EBP alpha mutations increase the proliferation of long-term hematopoietic stem cells (LT-HSCs) in a cell-intrinsic manner and override normal HSC homeostasis, leading to expansion of premalignant HSCs. However, such mutations impair myeloid programming of HSCs and block myeloid lineage commitment when homozygous. In contrast, N-terminal C/EBP alpha mutations are silent with regards to HSC expansion, but allow the formation of committed myeloid progenitors, the templates for leukemia-initiating cells. The combination of N- and C-terminal C/EBP alpha mutations incorporates both features, accelerating disease development and explaining the clinical prevalence of this configuration of CEBPA mutations.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Bereshchenko, Ox ...
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Mancini, Elena
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Moore, Susan
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Bilbao, Daniel
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Månsson, Robert
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Luc, Sidinh
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show more...
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Grover, Amit
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Jacobsen, Sten E ...
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Bryder, David
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Nerlov, Claus
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
- Articles in the publication
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Cancer Cell
- By the university
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Lund University