In Childhood Acute Lymphoblastic Leukemia, Blasts at Different Stages of Immunophenotypic Maturation Have Stem Cell Properties

Christoph le Viseur; Marc Hotfilder; Simon Bomken; Kerrie Wilson; Silja Röttgers; André Schrauder; Annegret Rosemann; Julie Irving; Ronald W. Stam; Leonard D. Shultz; Jochen Harbott; Heribert Jürgens; Martin Schrappe; Rob Pieters; Josef Vormoor

doi:10.1016/j.ccr.2008.05.015

In Childhood Acute Lymphoblastic Leukemia, Blasts at Different Stages of Immunophenotypic Maturation Have Stem Cell Properties

Christoph le Viseur, Marc Hotfilder, Simon Bomken, Kerrie Wilson, Silja Röttgers, André Schrauder, Annegret Rosemann, Julie Irving, Ronald W. Stam, Leonard D. Shultz, Jochen Harbott, Heribert Jürgens, Martin Schrappe, Rob Pieters, Josef Vormoor

Research output: Contribution to journal › Article › peer-review

234 Citations (Scopus)

Abstract

We examined the leukemic stem cell potential of blasts at different stages of maturation in childhood acute lymphoblastic leukemia (ALL). Human leukemic bone marrow was transplanted intrafemorally into NOD/scid mice. Cells sorted using the B precursor differentiation markers CD19, CD20, and CD34 were isolated from patient samples and engrafted mice before serial transplantation into primary or subsequent (up to quaternary) recipients. Surprisingly, blasts representative of all of the different maturational stages were able to reconstitute and reestablish the complete leukemic phenotype in vivo. Sorted blast populations mirrored normal B precursor cells with transcription of a number of stage-appropriate genes. These observations inform a model for leukemia-propagating stem cells in childhood ALL.

Original language	English
Pages (from-to)	47-58
Number of pages	12
Journal	Cancer Cell
Volume	14
Issue number	1
DOIs	https://doi.org/10.1016/j.ccr.2008.05.015
Publication status	Published - 8 Jul 2008
Externally published	Yes

Keywords

CELLCYCLE
STEMCELL

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10.1016/j.ccr.2008.05.015

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le Viseur, C., Hotfilder, M., Bomken, S., Wilson, K., Röttgers, S., Schrauder, A., Rosemann, A., Irving, J., Stam, R. W., Shultz, L. D., Harbott, J., Jürgens, H., Schrappe, M., Pieters, R., & Vormoor, J. (2008). In Childhood Acute Lymphoblastic Leukemia, Blasts at Different Stages of Immunophenotypic Maturation Have Stem Cell Properties. Cancer Cell, 14(1), 47-58. https://doi.org/10.1016/j.ccr.2008.05.015

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title = "In Childhood Acute Lymphoblastic Leukemia, Blasts at Different Stages of Immunophenotypic Maturation Have Stem Cell Properties",

abstract = "We examined the leukemic stem cell potential of blasts at different stages of maturation in childhood acute lymphoblastic leukemia (ALL). Human leukemic bone marrow was transplanted intrafemorally into NOD/scid mice. Cells sorted using the B precursor differentiation markers CD19, CD20, and CD34 were isolated from patient samples and engrafted mice before serial transplantation into primary or subsequent (up to quaternary) recipients. Surprisingly, blasts representative of all of the different maturational stages were able to reconstitute and reestablish the complete leukemic phenotype in vivo. Sorted blast populations mirrored normal B precursor cells with transcription of a number of stage-appropriate genes. These observations inform a model for leukemia-propagating stem cells in childhood ALL.",

keywords = "CELLCYCLE, STEMCELL",

author = "{le Viseur}, Christoph and Marc Hotfilder and Simon Bomken and Kerrie Wilson and Silja R{\"o}ttgers and Andr{\'e} Schrauder and Annegret Rosemann and Julie Irving and Stam, {Ronald W.} and Shultz, {Leonard D.} and Jochen Harbott and Heribert J{\"u}rgens and Martin Schrappe and Rob Pieters and Josef Vormoor",

note = "Funding Information: We thank Andy Hall and Olaf Heidenreich for critical comments and Karel Fiser for assistance with normalizing expression array data. This work was supported by Deutsche Jos{\'e} Carreras Leuk{\"a}mie-Stiftung e.V. grant R03/03 (to J.V.), by pump priming grants from the JGW Patterson Foundation and the North East Children's Cancer Research Fund (to J.V.), and in part by NIH Cancer Core grant CA34196 (to L.D.S.). ",

year = "2008",

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doi = "10.1016/j.ccr.2008.05.015",

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le Viseur, C, Hotfilder, M, Bomken, S, Wilson, K, Röttgers, S, Schrauder, A, Rosemann, A, Irving, J, Stam, RW, Shultz, LD, Harbott, J, Jürgens, H, Schrappe, M, Pieters, R & Vormoor, J 2008, 'In Childhood Acute Lymphoblastic Leukemia, Blasts at Different Stages of Immunophenotypic Maturation Have Stem Cell Properties', Cancer Cell, vol. 14, no. 1, pp. 47-58. https://doi.org/10.1016/j.ccr.2008.05.015

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AU - le Viseur, Christoph

AU - Hotfilder, Marc

AU - Bomken, Simon

AU - Wilson, Kerrie

AU - Röttgers, Silja

AU - Schrauder, André

AU - Rosemann, Annegret

AU - Irving, Julie

AU - Stam, Ronald W.

AU - Shultz, Leonard D.

AU - Harbott, Jochen

AU - Jürgens, Heribert

AU - Schrappe, Martin

AU - Pieters, Rob

AU - Vormoor, Josef

N1 - Funding Information: We thank Andy Hall and Olaf Heidenreich for critical comments and Karel Fiser for assistance with normalizing expression array data. This work was supported by Deutsche José Carreras Leukämie-Stiftung e.V. grant R03/03 (to J.V.), by pump priming grants from the JGW Patterson Foundation and the North East Children's Cancer Research Fund (to J.V.), and in part by NIH Cancer Core grant CA34196 (to L.D.S.).

PY - 2008/7/8

Y1 - 2008/7/8

N2 - We examined the leukemic stem cell potential of blasts at different stages of maturation in childhood acute lymphoblastic leukemia (ALL). Human leukemic bone marrow was transplanted intrafemorally into NOD/scid mice. Cells sorted using the B precursor differentiation markers CD19, CD20, and CD34 were isolated from patient samples and engrafted mice before serial transplantation into primary or subsequent (up to quaternary) recipients. Surprisingly, blasts representative of all of the different maturational stages were able to reconstitute and reestablish the complete leukemic phenotype in vivo. Sorted blast populations mirrored normal B precursor cells with transcription of a number of stage-appropriate genes. These observations inform a model for leukemia-propagating stem cells in childhood ALL.

AB - We examined the leukemic stem cell potential of blasts at different stages of maturation in childhood acute lymphoblastic leukemia (ALL). Human leukemic bone marrow was transplanted intrafemorally into NOD/scid mice. Cells sorted using the B precursor differentiation markers CD19, CD20, and CD34 were isolated from patient samples and engrafted mice before serial transplantation into primary or subsequent (up to quaternary) recipients. Surprisingly, blasts representative of all of the different maturational stages were able to reconstitute and reestablish the complete leukemic phenotype in vivo. Sorted blast populations mirrored normal B precursor cells with transcription of a number of stage-appropriate genes. These observations inform a model for leukemia-propagating stem cells in childhood ALL.

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IS - 1

ER -

In Childhood Acute Lymphoblastic Leukemia, Blasts at Different Stages of Immunophenotypic Maturation Have Stem Cell Properties

Abstract

Keywords

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