Piceatannol Induces Fetal Hemoglobin In Erythroid Progenitor Cells From Patients With Sickle Cell Disease

Background: We have identified the FOXO3-AMPK-AKT pathway as important to HbF regulation through unbiased analysis of whole exome sequencing from patients with sickle cell disease (SCD). Both AMPK and AKT are activated by phosphorylation; AMPK is a FOXO3 activator; AKT inhibits AMPK and FOXO3. We have also treated hematopoietic stem and progenitor cells (HSPCs) from patients with SCD with metformin, a known AMPK/FOXO3 activator, and produced a significant rise in HbF from 17.6% at baseline, to 44.9%. This data is the foundation for an IRB approved clinical trial of metformin in patients with hemoglobinopathies, enrolling patients now.