Variation in Gamma-Globin Expression before and after Induction with Hydroxyurea Associated with BCL11A, KLF1 and TAL1.
Where this comes from
- Record sourced from PubMed, PMID 26053062.
- Also identified by DOI 10.1371/journal.pone.0129431 and PMC identifier 4459969.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
The molecular mechanisms governing γ-globin expression in a subset of fetal hemoglobin (α2γ2: HbF) expressing red blood cells (F-cells) and the mechanisms underlying the variability of response to hydroxyurea induced γ-globin expression in the treatment of sickle cell disease are not completely understood. Here we analyzed intra-person clonal populations of basophilic erythroblasts (baso-Es) derived from bone marrow common myeloid progenitors in serum free cultures and report the level of fetal hemoglobin production in F-cells negatively correlates with expression of BCL11A, KLF1 and TAL1. We then examined the effects of hydroxyurea on these three transcription factors and conclude that a successful induction of γ-globin includes a reduction in BCL11A, KLF1 and TAL1 expression. These data suggests that expression changes in this transcription factor network modulate γ-globin expression in F-cells during steady state erythropoiesis and after induction with hydroxyurea.
Medical subject headings
- Basic Helix-Loop-Helix Proteins
- Carrier Proteins
- Hydroxyurea
- Kruppel-Like Transcription Factors
- Nuclear Proteins
- Proto-Oncogene Proteins
- gamma-Globins