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Acute B lymphoblastic leukaemia-propagating cells are present at high frequency in diverse lymphoblast populations

Lookup NU author(s): Dr Klaus Rehe, Kerrie Wilson, Dr Simon Bomken, Dr Daniel Williamson, Professor Julie Irving, Emeritus Professor Andy Hall, Professor Olaf Heidenreich, Professor Josef Vormoor

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Abstract

Leukaemia-propagating cells are more frequent in high-risk acute B lymphoblastic leukaemia than in many malignancies that follow a hierarchical cancer stem cell model. It is unclear whether this characteristic can be more universally applied to patients from non-high-risk sub-groups and across a broad range of cellular immunophenotypes. Here, we demonstrate in a wide range of primary patient samples and patient samples previously passaged through mice that leukaemia-propagating cells are found in all populations defined by high or low expression of the lymphoid differentiation markers CD10, CD20 or CD34. The frequency of leukaemia-propagating cells and their engraftment kinetics do not differ between these populations. Transcriptomic analysis of CD34high and CD34low blasts establishes their difference and their similarity to comparable normal progenitors at different stages of B-cell development. However, consistent with the functional similarity of these populations, expression signatures characteristic of leukaemia propagating cells in acute myeloid leukaemia fail to distinguish between the different populations. Together, these findings suggest that there is no stem cell hierarchy in acute B lymphoblastic leukaemia.


Publication metadata

Author(s): Rehe K, Wilson K, Bomken S, Williamson D, Irving J, den Boer ML, Stanulla M, Schrappe M, Hall AG, Heidenreich O, Vormoor J

Publication type: Article

Publication status: Published

Journal: EMBO Molecular Medicine

Year: 2013

Volume: 5

Issue: 1

Pages: 38-51

Print publication date: 11/12/2012

Date deposited: 07/02/2013

ISSN (print): 1757-4676

ISSN (electronic): 1757-4684

Publisher: Wiley-Blackwell Publishing Ltd.

URL: http://dx.doi.org/10.1002/emmm.201201703

DOI: 10.1002/emmm.201201703


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