WFRF:(Jaako Pekka)
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Hematopoietic Stem Cells Are Intrinsically Protected against MLL-ENL-Mediated Transformation.
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- Ugale, Amol (author)
- Lund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Department of Experimental Medical Science,Faculty of Medicine
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- Norddahl, Gudmundur (author)
- Lund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Avdelningen för molekylärmedicin och genterapi,Institutionen för laboratoriemedicin,Department of Experimental Medical Science,Faculty of Medicine,Division of Molecular Medicine and Gene Therapy,Department of Laboratory Medicine
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- Wahlestedt, Martin (author)
- Lund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Department of Experimental Medical Science,Faculty of Medicine
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- (creator_code:org_t)
- Elsevier BV, 2014
- 2014
- English.
- In: Cell Reports. - : Elsevier BV. - 2211-1247. ; 9:4, s. 1246-1255
- Journal article (peer-reviewed)
Abstract
Subject headings
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- Studies of developmental pathways of hematopoietic stem cells (HSCs) have defined lineage relationships throughout the blood system. This is relevant to acute myeloid leukemia (AML), where aggressiveness and therapeutic responsiveness can be influenced by the initial stage of transformation. To address this, we generated a mouse model in which the mixed-lineage leukemia/eleven-nineteen-leukemia (MLL-ENL) transcription factor can be conditionally activated in any cell type. We show that AML can originate from multiple hematopoietic progenitor subsets with granulocytic and monocytic potential, and that the normal developmental position of leukemia-initiating cells influences leukemic development. However, disease failed to arise from HSCs. Although it maintained or upregulated the expression of target genes associated with leukemic development, MLL-ENL dysregulated the proliferative and repopulating capacity of HSCs. Therefore, the permissiveness for development of AML may be associated with a narrower window of differentiation than was previously appreciated, and hijacking the self-renewal capacity of HSCs by a potent oncogene is insufficient for leukemic development.
Subject headings
- NATURVETENSKAP -- Biologi -- Cellbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Cell Biology (hsv//eng)
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- Jaako, Pekka
- Pronk, Kees-Jan
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- Soneji, Shamit
- Cammenga, Jörg
- Bryder, David
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