Investigation of FoxO3 dynamics during erythroblast development in β-thalassemia major

• DOI: 10.1371/journal.pone.0187610
• Publication Date: 2017-11-03T13:36:38Z
• Authors: Naruchit Thanutha...; Lalana Nuntakarn; Somponnat Sampatt...; Usanarat Anurathapan; Suphanun Phuphani...; Savichaya Pornpai...; Suparerk Borwornp...; Suradej Hongeng
• Keywords: FOXO3; Erythroblast; Ineffective erythropoiesis

The FoxO3 transcription factor is a key regulator of oxidative stress and erythroid maturation during erythropoiesis. In this study, we explored the involvement in severe β-thalassemia. Using primary CD34+ hematopoietic progenitor cells from patients with β-thalassemia major, successfully developed an vitro model ineffective Based on model, activity was quantified single using high throughput imaging flow cytometry. This study revealed significant reduction late stage erythroblast differentiation β-thalassemia, contrast to erythropoiesis normal that maintain persistent activation FoxO3. agreement decreased expression target genes also found decrease, concurrent elevated phosphorylation AKT, most clearly at differentiation. Our findings provide further evidence for terminal confirm modulation PI3K/AKT pathway as potential therapeutic strategy