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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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
State	Published - Jun 8 2015

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

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.",

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AU - Green, Nancy S.

AU - Driscoll, M. Catherine

AU - Bouhassira, Eric E.

N1 - Publisher Copyright: © 2015 Grieco et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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N2 - 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.

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

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