Variation in Gamma-Globin Expression before and after Induction with Hydroxyurea Associated with BCL11A, KLF1 and TAL1

• Published in: PloS one 2015-06, Vol.10 (6), p.e0129431
• Main Authors: Grieco, Amanda J, Billett, Henny H, Green, Nancy S, Driscoll, M Catherine, Bouhassira, Eric E
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Analysis; Animals; Basic Helix-Loop-Helix Transcription Factors - metabolism; Basophils - drug effects; Basophils - metabolism; Blood; Blood cells; Bone marrow; Carrier Proteins - metabolism; Cell cycle; Cells, Cultured; Child; Clone Cells; Erythroblasts; Erythroblasts - drug effects; Erythroblasts - metabolism; Erythrocytes; Erythropoiesis; Fetuses; gamma-Globins - genetics; gamma-Globins - metabolism; Gene expression; Gene Expression Regulation - drug effects; Hematology; Hemoglobin; Hemoglobins; Humans; Hydroxyurea; Hydroxyurea - pharmacology; Kruppel-Like Transcription Factors - genetics; Kruppel-Like Transcription Factors - metabolism; Medical treatment; Medicine; Mice; Middle Aged; Molecular chains; Molecular modelling; Nuclear Proteins - metabolism; Osteoprogenitor cells; Pediatrics; Proteins; Proto-Oncogene Proteins - metabolism; Repressor Proteins; Sickle cell anemia; Sickle cell disease; Stem cells; Stem Cells - cytology; Stem Cells - drug effects; Stem Cells - metabolism; T-Cell Acute Lymphocytic Leukemia Protein 1; Transcription factors; Young Adult
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0129431

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.