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.
authors.affiliation: Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York, United States of America.
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Grieco
authors.affiliation: Division of Hematology, Department of Medicine, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, New York, United States of America.
authors.forename: Henny H
authors.initials: HH
authors.lastname: Billett
authors.affiliation: Division of Pediatric Hematology/Oncology/Stem Cell Transplantation, Department of Pediatrics, Columbia University, New York, New York, United States of America.
authors.forename: Nancy S
authors.initials: NS
authors.lastname: Green
authors.affiliation: Department of Pediatrics, Division of Hematology-Oncology, AECOM, Bronx, New York, United States of America.
authors.forename: M Catherine
authors.initials: MC
authors.lastname: Driscoll
authors.affiliation: Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York, United States of America.
authors.forename: Eric E
authors.initials: EE
authors.lastname: Bouhassira
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D001491:Basophils / Q000187:drug effects / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D002648:Child; D002999:Clone Cells; D004900:Erythroblasts / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology*; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008875:Middle Aged; D009687:Nuclear Proteins / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D012097:Repressor Proteins; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D055815:Young Adult; D055545:gamma-Globins / Q000235:genetics* / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D002352:Carrier Proteins; D006918:Hydroxyurea; D051741:Kruppel-Like Transcription Factors; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D055545:gamma-Globins; C486563:BCL11A protein, human; C080774:erythroid Kruppel-like factor; C067143:TAL1 protein, human