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    Grist for the MLL: how do MLL oncogenic fusion proteins generate leukemia stem cells?

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    Authors
    Somervaille, Tim C P
    Cleary, Michael L
    Affiliation
    Cancer Research UK Leukaemia Biology Group, Paterson Institute for Cancer Research, Manchester, M20 4BX, UK.
    Issue Date
    2010-06
    
    Metadata
    Show full item record
    Abstract
    MLL fusion oncogenes are pathogenically associated with 5-10% of human acute leukemias. Through multiple interactions with chromatin regulatory factors, they convert a normal hematopoietic hierarchy into a leukemia cell hierarchy sustained at its apex by a population of inappropriately self-renewing myeloid cells termed leukemia stem cells (LSCs). Initiation of the aberrant leukemia cell hierarchy is associated with an abnormal epigenetic state at Hoxa and Meis1 loci, with concomitant high level Hoxa and Meis1 expression. This introduces at the level of the myeloblast, or thereabouts, a finite probability of self-renewal division where none previously existed. In contrast, differentiation-mediated exit of LSCs from the self-renewing compartment of the leukemia clone depends on the prevailing levels of the transcription factor Myb, which functions as part of an LSC maintenance program influenced, but not directly controlled, by Hoxa and Meis1. Critical biologic and molecular differences between self-renewing progenitor-like LSCs and hematopoietic stem cells could potentially be targeted by novel therapeutic strategies.
    Citation
    Grist for the MLL: how do MLL oncogenic fusion proteins generate leukemia stem cells? 2010, 91 (5):735-41 Int J Hematol
    Journal
    International Journal of Hematology
    URI
    http://hdl.handle.net/10541/109045
    DOI
    10.1007/s12185-010-0579-8
    PubMed ID
    20454944
    Type
    Article
    Language
    en
    ISSN
    1865-3774
    ae974a485f413a2113503eed53cd6c53
    10.1007/s12185-010-0579-8
    Scopus Count
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