Acute B lymphoblastic leukaemia-propagating cells are present at high frequency in diverse lymphoblast populations.
Bottom Line: 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.Together, these findings suggest that there is no stem cell hierarchy in acute B lymphoblastic leukaemia.
Affiliation: Newcastle Cancer Centre at the Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, UK.Show MeSH
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Mentions: 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 (le Viseur et al, 2008). One question that arose from these results was whether this was a generic finding indicating the absence of a stem cell hierarchy in B-cell precursor ALL or whether other candidate B-cell markers would allow enrichment of leukaemia-propagating activity. We therefore tested CD10 and CD20, surface molecules that are expressed in a maturation-dependent fashion during normal B-cell development (Fig 1) (van Zelm et al, 2005). Importantly, the patient samples used for these experiments no longer focus on infant ALL with MLL rearrangements, but reflect a wider range of different ALL subtypes, including high-risk Philadelphia chromosome-positive and BCR-ABL1-like ALL, intermediate risk ALL with no known cytogenetic risk factors and prognostically more favourable ALL with high hyperdiploidy (Table 1). The ability of purified cells to initiate the leukaemia was interrogated by intrafemoral injection into immunodeficient NSG mice. Engrafted leukaemia mirrored the original disease with enlarged spleens and infiltration of bone marrow, liver, kidneys and the central nervous system and by morphology and immunophenotype.
Affiliation: Newcastle Cancer Centre at the Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, UK.