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Stem Cell Reports. 2015 Jan 13;4(1):74-89. doi: 10.1016/j.stemcr.2014.10.012. Epub 2014 Nov 26.

Tracing dynamics and clonal heterogeneity of Cbx7-induced leukemic stem cells by cellular barcoding.

Author information

1
European Institute for the Biology of Ageing (ERIBA), Section Ageing Biology and Stem Cells, University Medical Centre Groningen, University of Groningen, Groningen 9700 AD, the Netherlands. Electronic address: k.klauke@umcg.nl.
2
European Institute for the Biology of Ageing (ERIBA), Section Ageing Biology and Stem Cells, University Medical Centre Groningen, University of Groningen, Groningen 9700 AD, the Netherlands.
3
European Institute for the Biology of Ageing (ERIBA), Section Ageing Biology and Stem Cells, University Medical Centre Groningen, University of Groningen, Groningen 9700 AD, the Netherlands. Electronic address: g.de.haan@umcg.nl.

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.

PMID:
25434821
PMCID:
PMC4297865
DOI:
10.1016/j.stemcr.2014.10.012
[Indexed for MEDLINE]
Free PMC Article

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