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

Rehe K, Wilson K, Bomken S, Williamson D, Irving J, den Boer ML, Staa M, Schrappe M, Hall AG, Heidenreich O, Vormoor J - EMBO Mol Med (2012)

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.

View Article: PubMed Central - PubMed

Affiliation: Newcastle Cancer Centre at the Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, UK.

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B-cell differentiation markers and engraftment potentialExpression of the cell surface antigens CD10, CD19, CD20 and CD34 during normal human B-cell development (van Zelm et al, 2005).Percentage of engrafting primary patient and primograft samples for the different populations (CD10low/high, CD20low/high, CD34low/high). Black bars provide the data for primary and white bars for primograft samples.Weighted mean of engraftment in mice transplanted with at least 1000 blasts sorted for CD10, CD20 or CD34 expression. The analysis takes into account that different numbers of mice were transplanted with cells from different samples. For data of engraftment of mice transplanted with cells sorted for expression of CD10 and CD20, see also Supporting Information Tables S1 and S2. The CD34 data are taken from the limiting dilutions experiments (Table 2) and include only the mice transplanted with 1000 cells.
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fig01: B-cell differentiation markers and engraftment potentialExpression of the cell surface antigens CD10, CD19, CD20 and CD34 during normal human B-cell development (van Zelm et al, 2005).Percentage of engrafting primary patient and primograft samples for the different populations (CD10low/high, CD20low/high, CD34low/high). Black bars provide the data for primary and white bars for primograft samples.Weighted mean of engraftment in mice transplanted with at least 1000 blasts sorted for CD10, CD20 or CD34 expression. The analysis takes into account that different numbers of mice were transplanted with cells from different samples. For data of engraftment of mice transplanted with cells sorted for expression of CD10 and CD20, see also Supporting Information Tables S1 and S2. The CD34 data are taken from the limiting dilutions experiments (Table 2) and include only the mice transplanted with 1000 cells.

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.


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

Rehe K, Wilson K, Bomken S, Williamson D, Irving J, den Boer ML, Staa M, Schrappe M, Hall AG, Heidenreich O, Vormoor J - EMBO Mol Med (2012)

B-cell differentiation markers and engraftment potentialExpression of the cell surface antigens CD10, CD19, CD20 and CD34 during normal human B-cell development (van Zelm et al, 2005).Percentage of engrafting primary patient and primograft samples for the different populations (CD10low/high, CD20low/high, CD34low/high). Black bars provide the data for primary and white bars for primograft samples.Weighted mean of engraftment in mice transplanted with at least 1000 blasts sorted for CD10, CD20 or CD34 expression. The analysis takes into account that different numbers of mice were transplanted with cells from different samples. For data of engraftment of mice transplanted with cells sorted for expression of CD10 and CD20, see also Supporting Information Tables S1 and S2. The CD34 data are taken from the limiting dilutions experiments (Table 2) and include only the mice transplanted with 1000 cells.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC3569652&req=5

fig01: B-cell differentiation markers and engraftment potentialExpression of the cell surface antigens CD10, CD19, CD20 and CD34 during normal human B-cell development (van Zelm et al, 2005).Percentage of engrafting primary patient and primograft samples for the different populations (CD10low/high, CD20low/high, CD34low/high). Black bars provide the data for primary and white bars for primograft samples.Weighted mean of engraftment in mice transplanted with at least 1000 blasts sorted for CD10, CD20 or CD34 expression. The analysis takes into account that different numbers of mice were transplanted with cells from different samples. For data of engraftment of mice transplanted with cells sorted for expression of CD10 and CD20, see also Supporting Information Tables S1 and S2. The CD34 data are taken from the limiting dilutions experiments (Table 2) and include only the mice transplanted with 1000 cells.
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.

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.

View Article: PubMed Central - PubMed

Affiliation: Newcastle Cancer Centre at the Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, UK.

Show MeSH
Related in: MedlinePlus