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.
Highlights
Based on the pioneering work by Till and McCulloch (Till & McCulloch, 1961), normal haematopoiesis is known to be (1) Newcastle Cancer Centre at the Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, UK (2) Great North Children’s Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK (3) Department of Pediatric Oncology and Hematology, Erasmus MC-Sophia Children’s Hospital, Rotterdam, The Netherlands (4) Department of Pediatrics, University Medical Center Schleswig-Holstein, Campus Kiel, Kiel, Germany (5) North of England Stem Cell Institute, Newcastle University, Newcastle upon Tyne, UKThis hierarchical cancer stem cell model has been explored in other cancer types using similar xenotransplantation models (Bomken et al, 2010)
Immunophenotypic diversity and malleability of leukaemiapropagating cells In our previous experiments, we had shown that phenotypically diverse ALL blasts, mainly characterized by expression of CD19 and CD34, are able to propagate the human leukaemia in immunodeficient mice
As the strongest evidence for a rare, phenotypically immature leukaemia stem cell population in B-ALL came from experiments with Philadelphia chromosome-positive ALL (Castor et al, 2005; Cobaleda et al, 2000; Hotfilder et al, 2005), we primarily focused on patients, which were either BCR-ABL1positive or demonstrated a BCR-ABL1-like expression signature
Summary
Based on the pioneering work by Till and McCulloch (Till & McCulloch, 1961), normal haematopoiesis is known to be (1) Newcastle Cancer Centre at the Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, UK (2) Great North Children’s Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK (3) Department of Pediatric Oncology and Hematology, Erasmus MC-Sophia Children’s Hospital, Rotterdam, The Netherlands (4) Department of Pediatrics, University Medical Center Schleswig-Holstein, Campus Kiel, Kiel, Germany (5) North of England Stem Cell Institute, Newcastle University, Newcastle upon Tyne, UK This hierarchical cancer stem cell model has been explored in other cancer types using similar xenotransplantation models (Bomken et al, 2010). Stem cell phenotypes and frequencies may change during tumour development and progression, consistent with the model of clonal evolution (Anderson et al, 2011; Notta et al, 2011)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
