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

doi:10.1371/journal.pone.0129431

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

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12 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 language	English (US)
Article number	e0129431
Journal	PloS one
Volume	10
Issue number	6
DOIs	https://doi.org/10.1371/journal.pone.0129431
Publication status	Published - Jun 8 2015

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ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)
Agricultural and Biological Sciences(all)
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Cite this

Grieco, A. J., Billett, H. H., Green, N. S., Driscoll, M. C., & Bouhassira, E. E. (2015). Variation in gamma-globin expression before and after induction with hydroxyurea associated with BCL11A, KLF1 and TAL1. PloS one, 10(6), [e0129431]. https://doi.org/10.1371/journal.pone.0129431

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