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

• DOI: 10.1016/j.stemcr.2014.10.012
• Publication Date: 2014-11-26T21:43:43Z
• Authors: Karin Klauke; Mathilde J.C. Bro...; Ellen Weersing; Albertina Dethmer...; Martha Ritsema; Marta Vilà González; Erik Zwart; Leonid V. Bystrykh; Gerald de Haan
• Keywords: 0301 basic medicine; Medicine (General); QH301-705.5; Gene Expression; Bone Marrow Cells; ACUTE MYELOID-LEUKEMIA; RELAPSE; Article; Immunophenotyping; Clonal Evolution; Mice; 03 medical and health sciences; R5-920; Animals; Cluster Analysis; Biology (General); ACUTE LYMPHOBLASTIC-LEUKEMIA; Polycomb Repressive Complex 1; LINEAGE SWITCH; Leukemia; CHRONIC LYMPHOCYTIC-LEUKEMIA; MUTATIONS; Gene Expression Profiling; EVOLUTION; SELF-RENEWAL; Disease Models, Animal; HIERARCHY; Cell Transformation, Neoplastic; Phenotype; PATTERNS; Disease Progression; Neoplastic Stem Cells

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.