Figure 6
Figure 6. CNTO 530 uniquely induces the sustained expansion of a bone marrow–resident KitnegCD71highTer119neg E2 progenitor pool. (A) Based in part on recent ex vivo analyses of murine bone marrow erythroid progenitor pools,32,34,35 a course of stepwise development can be defined as a Kitpos CD71highTer119neg → Kitneg CD71highTer119neg → Kitneg CD71highTer119pos cell progression (ie, stages E1 → E2 → E3). (B) At steady state, stage-E3 bone marrow progenitors were predominant as assayed via costaining for Kit, CD71, and Ter119 markers, and gating-off red blood cells (RBCs) and reticulocytes. E1 and E2 progenitors were assayed by gating off Ter119pos cells and on Kitpos vs Kitneg CD71high cells. Each symbol in each set represents the value for an independently treated and analyzed mouse. (C) CNTO 530 uniquely and markedly expands stage-E2 bone marrow progenitors: C57BL/6 mice were dosed with either CNTO 530 (0.2 μg/mouse gram-weight) or darbepoietin (0.015 μg/mouse gram-weight). At days 2.5 and 4.5, levels of E1, E2, and E3 progenitors were then determined via flow cytometry. Graphed values (top panel) are means ± SE (n = 3). (D) Primary flow cytometry data illustrate CNTO 530 expansion of stage-E2 erythroid progenitors within bone marrow (here at day 4.5 after dosing with either CNTO 530, darbepoietin, or saline).

CNTO 530 uniquely induces the sustained expansion of a bone marrow–resident KitnegCD71highTer119neg E2 progenitor pool. (A) Based in part on recent ex vivo analyses of murine bone marrow erythroid progenitor pools,32,34,35  a course of stepwise development can be defined as a Kitpos CD71highTer119neg → Kitneg CD71highTer119neg → Kitneg CD71highTer119pos cell progression (ie, stages E1 → E2 → E3). (B) At steady state, stage-E3 bone marrow progenitors were predominant as assayed via costaining for Kit, CD71, and Ter119 markers, and gating-off red blood cells (RBCs) and reticulocytes. E1 and E2 progenitors were assayed by gating off Ter119pos cells and on Kitpos vs Kitneg CD71high cells. Each symbol in each set represents the value for an independently treated and analyzed mouse. (C) CNTO 530 uniquely and markedly expands stage-E2 bone marrow progenitors: C57BL/6 mice were dosed with either CNTO 530 (0.2 μg/mouse gram-weight) or darbepoietin (0.015 μg/mouse gram-weight). At days 2.5 and 4.5, levels of E1, E2, and E3 progenitors were then determined via flow cytometry. Graphed values (top panel) are means ± SE (n = 3). (D) Primary flow cytometry data illustrate CNTO 530 expansion of stage-E2 erythroid progenitors within bone marrow (here at day 4.5 after dosing with either CNTO 530, darbepoietin, or saline).

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