The Bcl-xL response to chronic stress and toacute-on-chronicstress. (A) Bcl-xL expression in mouse models of erythropoietic stress (red symbols) and matched controls (blue symbols), measured in freshly explanted tissue. Each data point is mean ± SEM of 2 to 4 mice. There were no statistically significant differences between chronic stress and control mice. (B) Representative experiment showing Bim expression in β-thalassemia mice in spleen (top) and BM (bottom). Two wild-type (black symbols) and 1 β-thalassemia mouse (red symbols) are shown. (C) The Bcl-xL response to an acute-on-chronic stimulus. Bcl-xL was measured in spleen and BM erythroblasts in β-thalassemia and matched control mice, 18 hours after a single injection of either Epo (300 U/25 g, red symbols) or saline (blue symbols). Data points are mean ± SEM of n = 3 to 4 mice. Representative of 4 independent experiments. There were statistically significant differences in Bcl-xL between Epo and saline injections in wild-type spleen ProE (P = .025, 2-tailed t test, unequal variance), EryA (P = .0009), EryB (P = .01), and EryC (P = .006); in β-thalassemia spleen EryA (P = .0004), EryB (P = .004), and EryC (P = .03); in wild-type BM EryA, EryB, and EryC (P ≤ .0005); and in β-thalassemia BM EryA, EryB (P < .0005), and EryC (P = .025). The increase in spleen EryA Bcl-xL was significantly higher (P = .023) in wild-type mice than in β-thalassemia mice. (D) The Bcl-xL response to 3 consecutive Epo injections. Wild-type mice were injected at time points 0, 24, and 48 hours with either Epo (300 U/25 g, indicated with arrowheads) or with saline. Bcl-xL in spleen EryA was assayed by flow cytometry in 2 mice for each treatment, 18 hours after each injection.
