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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow Cells / metabolism
  • Bone Marrow Cells / pathology
  • Cell Transformation, Neoplastic / genetics
  • Clonal Evolution / genetics*
  • Cluster Analysis
  • Disease Models, Animal
  • Disease Progression
  • Gene Expression
  • Gene Expression Profiling
  • Immunophenotyping
  • Leukemia / genetics*
  • Leukemia / pathology
  • Mice
  • Neoplastic Stem Cells / metabolism*
  • Neoplastic Stem Cells / pathology
  • Phenotype
  • Polycomb Repressive Complex 1 / genetics*

Substances

  • CBX7 protein, human
  • Polycomb Repressive Complex 1

Associated data

  • GEO/GSE56820