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 for this work

    Research output: Contribution to journalArticleAcademicpeer-review

    14 Citations (Scopus)
    324 Downloads (Pure)

    Abstract

    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.

    Original languageEnglish
    Pages (from-to)74-89
    Number of pages16
    JournalStem Cell Reports
    Volume4
    Issue number1
    DOIs
    Publication statusPublished - 13-Jan-2015

    Keywords

    • ACUTE MYELOID-LEUKEMIA
    • ACUTE LYMPHOBLASTIC-LEUKEMIA
    • CHRONIC LYMPHOCYTIC-LEUKEMIA
    • LINEAGE SWITCH
    • SELF-RENEWAL
    • EVOLUTION
    • MUTATIONS
    • HIERARCHY
    • PATTERNS
    • RELAPSE

    Fingerprint

    Dive into the research topics of 'Tracing Dynamics and Clonal Heterogeneity of Cbx7-Induced Leukemic Stem Cells by Cellular Barcoding'. Together they form a unique fingerprint.

    Cite this