Mitoxantrone ameliorates ineffective erythropoiesis in a ß-thalassemia intermedia mouse model.
Blood Adv
; 8(15): 4017-4024, 2024 Aug 13.
Article
in En
| MEDLINE
| ID: mdl-38861356
ABSTRACT
ABSTRACT ß-thalassemia is a condition characterized by reduced or absent synthesis of ß-globin resulting from genetic mutations, leading to expanded and ineffective erythropoiesis. Mitoxantrone has been widely used clinically as an antitumor agent considering its ability to inhibit cell proliferation. However, its therapeutic effect on expanded and ineffective erythropoiesis in ß-thalassemia is untested. We found that mitoxantrone decreased α-globin precipitates and ameliorated anemia, splenomegaly, and ineffective erythropoiesis in the HbbTh3/+ mouse model of ß-thalassemia intermedia. The partially reversed ineffective erythropoiesis is a consequence of effects on autophagy as mitochondrial retention and protein levels of mTOR, P62, and LC3 in reticulocytes decreased in mitoxantrone-treated HbbTh3/+ mice. These data provide significant preclinical evidence for targeting autophagy as a novel therapeutic approach for ß-thalassemia.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Mitoxantrone
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Beta-Thalassemia
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Disease Models, Animal
/
Erythropoiesis
Limits:
Animals
Language:
En
Journal:
Blood Adv
Year:
2024
Document type:
Article