Hydroxyurea reduces the levels of the fetal <i>globin</i> gene repressors ZBTB7A/LRF and BCL11A in erythroid cells <i>in vitro</i>.

ABSTRACT:

Objectives

Hydroxyurea (HU) is the most widely used therapy for adults and children with sickle cell disease (SCD). It is believed to act largely by inducing the transcription of fetal γ-globin genes to generate fetal hemoglobin (HbF), which inhibits the pathological polymerization of sickle hemoglobin (HbS). The mechanisms by which hydroxyurea elevates HbF are unclear. We explored the hypothesis that hydroxyurea induces HbF expression by inhibiting the expression of 2 γ-globin gene repressors, BCL11A and ZBTB7A (also known as LRF), which normally bind the γ-globin gene promoters to inhibit their expression after birth.

Methods

We treated immortalized murine erythroleukemia cells and normal human donor CD34⁺ hematopoietic stem and progenitor c

SUBMITTER: Martyn GE 

PROVIDER: S-EPMC12039817 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature