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

PloS One
Naruchit ThanuthanakhunSuradej Hongeng

Abstract

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

References

Aug 3, 2007·The Journal of Clinical Investigation·Dragan MarinkovicSaghi Ghaffari
Mar 29, 2008·Cell Stem Cell·Kana MiyamotoAtsushi Hirao
Mar 26, 2009·Current Opinion in Hematology·Stefano Rivella
Jan 26, 2010·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Antonio Cao, Renzo Galanello
Nov 16, 2010·Hematology/oncology Clinics of North America·Eugene Khandros, Mitchell J Weiss
Jan 29, 2011·Blood·Alison T Merryweather-ClarkeKathryn J H Robson
May 31, 2011·Biochimica Et Biophysica Acta·Melissa DobsonGuri Tzivion
Jun 29, 2011·Biochimica Et Biophysica Acta·Guri TzivionGopalakrishnan Ramakrishnan
Jul 26, 2011·Blood Cells, Molecules & Diseases·Amporn LeecharoenkiatDuncan R Smith
Feb 8, 2013·Nature·Matthew R WarrEmmanuelle Passegué
Apr 23, 2013·TheScientificWorldJournal·Jean-Antoine RibeilOlivier Hermine
Jun 27, 2013·Frontiers in Physiology·Judith Hagenbuchner, Michael J Ausserlechner
Nov 10, 2013·Oxidative Medicine and Cellular Longevity·Lucia De FranceschiFranco Turrini
Jun 27, 2014·American Journal of Hematology·Xin ZhangSaghi Ghaffari
Feb 18, 2015·International Journal of Molecular Sciences·Jieying ZhangXiuli An
Apr 7, 2015·Biochemical and Biophysical Research Communications·Hai WangXiangdong Fang
Apr 15, 2015·Blood·Sachith MettanandaDouglas R Higgs
Jun 10, 2015·Nature Reviews. Nephrology·Mark J Koury, Volker H Haase
Jul 22, 2016·British Journal of Haematology·Raymond Liang, Saghi Ghaffari
Oct 21, 2016·American Journal of Hematology·Alexandros MakisErsi Voskaridou

❮ Previous
Next ❯

Citations

May 22, 2018·Current Opinion in Hematology·Vijay Menon, Saghi Ghaffari
May 26, 2020·Hemoglobin·Magdalena M TeránBlanca A Issé
Mar 18, 2021·Blood Reviews·Priya Hariharan, Anita Nadkarni
Aug 17, 2021·Journal of Clinical Laboratory Analysis·Haiwei WangLiangpu Xu

❮ Previous
Next ❯

Methods Mentioned

BETA
leukapheresis
flow cytometry
protein assay
PCR
flow cytometry gating
light microscopy
nuclear translocation

Software Mentioned

IDEAS
OrthoE

Related Concepts

Related Feeds

Anemia

Anemia develops when your blood lacks enough healthy red blood cells. Anemia of inflammation (AI, also called anemia of chronic disease) is a common, typically normocytic, normochromic anemia that is caused by an underlying inflammatory disease. Here is the latest research on anemia.

AKT Pathway

This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.

Blood And Marrow Transplantation

The use of hematopoietic stem cell transplantation or blood and marrow transplantation (bmt) is on the increase worldwide. BMT is used to replace damaged or destroyed bone marrow with healthy bone marrow stem cells. Here is the latest research on bone and marrow transplantation.