title: Tracing dynamics and clonal heterogeneity of Cbx7-induced leukemic stem cells by cellular barcoding.
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.
authors.affiliation: 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.
authors.forename: Karin
authors.initials: K
authors.lastname: Klauke
authors.affiliation: 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.
authors.forename: Mathilde J C
authors.initials: MJC
authors.lastname: Broekhuis
authors.affiliation: 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.
authors.forename: Ellen
authors.initials: E
authors.lastname: Weersing
authors.affiliation: 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.
authors.forename: Albertina
authors.initials: A
authors.lastname: Dethmers-Ausema
authors.affiliation: 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.
authors.forename: Martha
authors.initials: M
authors.lastname: Ritsema
authors.affiliation: 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.
authors.forename: Marta Vilà
authors.initials: MV
authors.lastname: González
authors.affiliation: 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.
authors.forename: Erik
authors.initials: E
authors.lastname: Zwart
authors.affiliation: 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.
authors.forename: Leonid V
authors.initials: LV
authors.lastname: Bystrykh
authors.affiliation: 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.
authors.forename: Gerald
authors.initials: G
authors.lastname: de Haan
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D060965:Clonal Evolution / Q000235:genetics*; D016000:Cluster Analysis; D004195:Disease Models, Animal; D018450:Disease Progression; D015870:Gene Expression; D020869:Gene Expression Profiling; D016130:Immunophenotyping; D007938:Leukemia / Q000235:genetics* / Q000473:pathology; D051379:Mice; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D010641:Phenotype; D063150:Polycomb Repressive Complex 1 / Q000235:genetics*
chemical_list: C503627:CBX7 protein, human; D063150:Polycomb Repressive Complex 1