Tracing Dynamics and Clonal Heterogeneity of Cbx7-Induced Leukemic Stem Cells by Cellular Barcoding

Karin Klauke*, Mathilde J. C. Broekhuis, Ellen Weersing, Albertina Dethmers-Ausema, Martha Ritsema, Marta Vila Gonzalez, Erik Zwart, Leonid V. Bystrykh, Gerald de Haan

*Corresponding author voor dit werk

    Onderzoeksoutput: ArticleAcademicpeer review

    14 Citaten (Scopus)
    336 Downloads (Pure)

    Samenvatting

    Accurate monitoring of tumor dynamics and leukemic stem cell (LSC) heterogeneity is important for the development of personalized cancer therapies. In this study, we experimentally induced distinct types of leukemia in mice by enforced expression of Cbx7. Simultaneous cellular barcoding allowed for thorough analysis of leukemias at the clonal level and revealed high and unpredictable tumor complexity. Multiple LSC clones with distinct leukemic properties coexisted. Some of these clones remained dormant but bore leukemic potential, as they progressed to full-blown leukemia after challenge. LSC clones could retain multilineage differentiation capacities, where one clone induced phenotypically distinct leukemias. Beyond a detailed insight into CBX7-driven leukemic biology, our model is of general relevance for the understanding of tumor dynamics and clonal evolution.

    Originele taal-2English
    Pagina's (van-tot)74-89
    Aantal pagina's16
    TijdschriftStem Cell Reports
    Volume4
    Nummer van het tijdschrift1
    DOI's
    StatusPublished - 13-jan.-2015

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