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Molecular mechanisms of fetal hemoglobin induction in eritroblasts of patients with bO/bO Thalassemia and in heterozygous individuals with non-deletional hereditary persistence of fetal hemoglobin (Brazilian type)

Grant number: 18/01367-9
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): June 01, 2018
Effective date (End): February 28, 2021
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Fernando Ferreira Costa
Grantee:Flávia Peixoto Albuquerque
Home Institution: Centro de Hematologia e Hemoterapia (HEMOCENTRO). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Associated research grant:14/00984-3 - Red blood cell disorders: pathophysiology and new therapeutic approaches, AP.TEM

Abstract

Fetal hemoglobin consists essentially of two alpha chains and of two gamma chains produced during the fetal period and its synthesis loses its dominance over the first six months of life after birth, gradually being replaced by adult hemoglobin. The regulation of fetal hemoglobin production is of scientific importance because it contributes to the understanding of the mechanisms of genes regulation involved in the synthesis of gamma globin chains. 'F cells' are a small fraction of red blood cells that are originated from immature erythroid progenitor’s cells. Precursors of such cells maintain the production of HbF, by persistent activation of gamma globin genes (g), leading to F reticulocytes and then mature F cells, which determine the amount of fetal hemoglobin available in the bloodstream. So far, the researchers have not identified which factors lead to fetal hemoglobin accumulation in F cells, despite they are important for maintaining the appropriate level of circulating red blood cells in patients with Hemoglobinopathies. F cell studies may provide a new therapeutic approach, in addition to inductors of fetal hemoglobin synthesis already known and to minimize recurrent blood transfusions. A better understanding of markers associated with fetal hemoglobin through variable synthesis of red blood cells is of scientific interest, since it can contribute to the understanding of the genes regulation mechanisms involved in the synthesis of globin chains, which to date have not been completely elucidated. (AU)