Hematopoietic Stem Cells Are Intrinsically Protected against MLL-ENL-Mediated Transformation.
Författare
Summary, in English
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.
Avdelning/ar
- Hematopoietic and immunologic developement
- Institutionen för experimentell medicinsk vetenskap
- Avdelningen för molekylärmedicin och genterapi
- BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
- StemTherapy: National Initiative on Stem Cells for Regenerative Therapy
Publiceringsår
2014
Språk
Engelska
Sidor
1246-1255
Publikation/Tidskrift/Serie
Cell Reports
Volym
9
Issue
4
Fulltext
Länkar
Dokumenttyp
Artikel i tidskrift
Förlag
Cell Press
Ämne
- Cell Biology
Status
Published
Forskningsgrupp
- Hematopoietic and immunologic developement
ISBN/ISSN/Övrigt
- ISSN: 2211-1247