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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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Engraftment kinetics of purified B-ALL subpopulation as assessed by sequential bone marrow puncturesMice from all limiting dilution experiments were pooled, as the number of mice in each individual transplantation experiment was too low for the analysis. Data are mean percentage of engraftment with bars showing standard error of the mean.A,B. Engraftment kinetics of CD10high and CD10low cells after transplantation of 100 (n = 4) or 1000–2000 blasts (n ≥ 4).C,D. Engraftment kinetics of CD20high and CD20low cells after transplantation of 100–300 (n ≥ 8) or 500–3000 blasts (n ≥ 21).E,F. Engraftment kinetics of CD34high and CD34low cells after transplantation of 100 (n ≥ 6, last points n = 2 for CD34high and n = 3 for CD34low) or 1000 blasts (n ≥ 9).
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fig04: Engraftment kinetics of purified B-ALL subpopulation as assessed by sequential bone marrow puncturesMice from all limiting dilution experiments were pooled, as the number of mice in each individual transplantation experiment was too low for the analysis. Data are mean percentage of engraftment with bars showing standard error of the mean.A,B. Engraftment kinetics of CD10high and CD10low cells after transplantation of 100 (n = 4) or 1000–2000 blasts (n ≥ 4).C,D. Engraftment kinetics of CD20high and CD20low cells after transplantation of 100–300 (n ≥ 8) or 500–3000 blasts (n ≥ 21).E,F. Engraftment kinetics of CD34high and CD34low cells after transplantation of 100 (n ≥ 6, last points n = 2 for CD34high and n = 3 for CD34low) or 1000 blasts (n ≥ 9).

Mentions: Next, we tested the engraftment kinetics of the different subpopulations. To this end, we determined the leukaemic infiltration produced by CD10-, CD20- and CD34-sorted blasts over time using sequential bone marrow punctures. In order to achieve sufficient numbers of mice at each time point, all engrafted mice transplanted with either 100–300 cells or 500–3000 cells were pooled for this analysis. Each of the population engrafted with similar kinetics (Fig 4).


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)

Engraftment kinetics of purified B-ALL subpopulation as assessed by sequential bone marrow puncturesMice from all limiting dilution experiments were pooled, as the number of mice in each individual transplantation experiment was too low for the analysis. Data are mean percentage of engraftment with bars showing standard error of the mean.A,B. Engraftment kinetics of CD10high and CD10low cells after transplantation of 100 (n = 4) or 1000–2000 blasts (n ≥ 4).C,D. Engraftment kinetics of CD20high and CD20low cells after transplantation of 100–300 (n ≥ 8) or 500–3000 blasts (n ≥ 21).E,F. Engraftment kinetics of CD34high and CD34low cells after transplantation of 100 (n ≥ 6, last points n = 2 for CD34high and n = 3 for CD34low) or 1000 blasts (n ≥ 9).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig04: Engraftment kinetics of purified B-ALL subpopulation as assessed by sequential bone marrow puncturesMice from all limiting dilution experiments were pooled, as the number of mice in each individual transplantation experiment was too low for the analysis. Data are mean percentage of engraftment with bars showing standard error of the mean.A,B. Engraftment kinetics of CD10high and CD10low cells after transplantation of 100 (n = 4) or 1000–2000 blasts (n ≥ 4).C,D. Engraftment kinetics of CD20high and CD20low cells after transplantation of 100–300 (n ≥ 8) or 500–3000 blasts (n ≥ 21).E,F. Engraftment kinetics of CD34high and CD34low cells after transplantation of 100 (n ≥ 6, last points n = 2 for CD34high and n = 3 for CD34low) or 1000 blasts (n ≥ 9).
Mentions: Next, we tested the engraftment kinetics of the different subpopulations. To this end, we determined the leukaemic infiltration produced by CD10-, CD20- and CD34-sorted blasts over time using sequential bone marrow punctures. In order to achieve sufficient numbers of mice at each time point, all engrafted mice transplanted with either 100–300 cells or 500–3000 cells were pooled for this analysis. Each of the population engrafted with similar kinetics (Fig 4).

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