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

doi:10.1016/j.stemcr.2014.10.012

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 journal › Article › Academic › peer-review

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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 language	English
Pages (from-to)	74-89
Number of pages	16
Journal	Stem Cell Reports
Volume	4
Issue number	1
DOIs	https://doi.org/10.1016/j.stemcr.2014.10.012
Publication status	Published - 13-Jan-2015

Keywords

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

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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.",

keywords = "ACUTE MYELOID-LEUKEMIA, ACUTE LYMPHOBLASTIC-LEUKEMIA, CHRONIC LYMPHOCYTIC-LEUKEMIA, LINEAGE SWITCH, SELF-RENEWAL, EVOLUTION, MUTATIONS, HIERARCHY, PATTERNS, RELAPSE",

author = "Karin Klauke and Broekhuis, {Mathilde J. C.} and Ellen Weersing and Albertina Dethmers-Ausema and Martha Ritsema and Gonzalez, {Marta Vila} and Erik Zwart and Bystrykh, {Leonid V.} and {de Haan}, Gerald",

year = "2015",

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doi = "10.1016/j.stemcr.2014.10.012",

language = "English",

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journal = "Stem Cell Reports",

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T1 - Tracing Dynamics and Clonal Heterogeneity of Cbx7-Induced Leukemic Stem Cells by Cellular Barcoding

AU - Klauke, Karin

AU - Broekhuis, Mathilde J. C.

AU - Weersing, Ellen

AU - Dethmers-Ausema, Albertina

AU - Ritsema, Martha

AU - Gonzalez, Marta Vila

AU - Zwart, Erik

AU - Bystrykh, Leonid V.

AU - de Haan, Gerald

PY - 2015/1/13

Y1 - 2015/1/13

N2 - 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.

AB - 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.

KW - ACUTE MYELOID-LEUKEMIA

KW - ACUTE LYMPHOBLASTIC-LEUKEMIA

KW - CHRONIC LYMPHOCYTIC-LEUKEMIA

KW - LINEAGE SWITCH

KW - SELF-RENEWAL

KW - EVOLUTION

KW - MUTATIONS

KW - HIERARCHY

KW - PATTERNS

KW - RELAPSE

U2 - 10.1016/j.stemcr.2014.10.012

DO - 10.1016/j.stemcr.2014.10.012

M3 - Article

C2 - 25434821

SN - 2213-6711

VL - 4

SP - 74

EP - 89

JO - Stem Cell Reports

JF - Stem Cell Reports

IS - 1

ER -

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

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Keywords

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