American Society of Hematology

Figure 5

$Figure 5. Systemic proteasome inhibition by bortezomib impairs both thalassemic and normal erythropoiesis in vivo. (A) Scheme for bortezomib dosing in wild-type and Th3/+ mice. (B) Proteasome activity in erythrocytes from mice 24 hours after treatment with 1.0 mg/kg of bortezomib. Activity, normalized to total protein, was measured by fluorescence release from Suc-LLVY-AMC proteasome substrate and normalized to control treated mice; n = 3 mice/group. **P < .01 versus control (CTRL). (C) RBC counts of +/+ or Th3/+ mice treated with vehicle or 1.0 mg/kg of bortezomib for 2 weeks; n = 10 mice/group. (D) RBC counts of +/+ or Th3/+ mice treated with vehicle or 1.0 mg/kg of bortezomib for 5 weeks; n = 6 mice/group. *P < .05; **P < .01; ***P < .001. (E) Spleen weight normalized to total body weight in bortezomib-treated and control mice n = 6 mice/group. *P < .05; ***P < .001. (F) Pulse-chase analysis of insoluble α-globin in reticulocytes from control or bortezomib-treated Th3/+ mice. (G) Coomassie-stained insoluble globin aggregates (top) from equal numbers of circulating erythrocytes from wild-type or Th3/+ mice treated with vehicle or bortezomib at 1.0 mg/kg. Soluble fractions are included as loading controls (bottom).$

Systemic proteasome inhibition by bortezomib impairs both thalassemic and normal erythropoiesis in vivo. (A) Scheme for bortezomib dosing in wild-type and Th3/+ mice. (B) Proteasome activity in erythrocytes from mice 24 hours after treatment with 1.0 mg/kg of bortezomib. Activity, normalized to total protein, was measured by fluorescence release from Suc-LLVY-AMC proteasome substrate and normalized to control treated mice; n = 3 mice/group. **P < .01 versus control (CTRL). (C) RBC counts of +/+ or Th3/+ mice treated with vehicle or 1.0 mg/kg of bortezomib for 2 weeks; n = 10 mice/group. (D) RBC counts of +/+ or Th3/+ mice treated with vehicle or 1.0 mg/kg of bortezomib for 5 weeks; n = 6 mice/group. *P < .05; **P < .01; ***P < .001. (E) Spleen weight normalized to total body weight in bortezomib-treated and control mice n = 6 mice/group. *P < .05; ***P < .001. (F) Pulse-chase analysis of insoluble α-globin in reticulocytes from control or bortezomib-treated Th3/+ mice. (G) Coomassie-stained insoluble globin aggregates (top) from equal numbers of circulating erythrocytes from wild-type or Th3/+ mice treated with vehicle or bortezomib at 1.0 mg/kg. Soluble fractions are included as loading controls (bottom).

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