Variation in gamma-globin expression before and after induction with hydroxyurea associated with BCL11A, KLF1 and TAL1

Amanda J. Grieco, Henny H. Billett, Nancy S. Green, M. Catherine Driscoll, Eric E. Bouhassira

Research output: Contribution to journalArticle

13 Scopus citations

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.

Original languageEnglish (US)
Article numbere0129431
JournalPloS one
Volume10
Issue number6
DOIs
StatePublished - Jun 8 2015

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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