title: Study on Hydroxyurea Response in Hemoglobinopathies Patients Using Genetic Markers and Liquid Erythroid Cultures.
abstract: Increased expression of fetal hemoglobin (HbF) may ameliorate the clinical course of hemoglobinopathies. Hydroxyurea (HU) is the only inducer approved for the treatment of these diseases able to stimulate HbF production but patients' response is highly variable indicating the utility of the identification of pharmacogenomic biomarkers in order to predict pharmacological treatment efficacy. To date few studies to evaluate the role of genetic determinants in HU response have been conducted showing contradictory results. In this study we analyzedBCL11A, GATA-1, KLF-1genes and γ-globin promoter in 60 alleles from 30 hemoglobinopathies patients under HU treatment to assess the role of these markers in HU response. We did not find any association between these genetic determinants and HU response. Before treatment started, the same patients were analyzedin vitrousing liquid erythroid cultures in a test able to predict their response to HU. The results of our analysis confirm the absence of pharmacogenomic biomarker associated to HU response indicating that, the quantification of γ-globin mRNA fold increase remains the only method able to predictin vivopatients response to the drug.
authors.affiliation: Department of Oncology and Hematology, U.O.C. Hematology for Rare Blood and of Hematopoietic Organs Diseases, A.O. Reunited Hospitals Villa Sofia-Cervello , Palermo, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Sclafani
authors.affiliation: Department of Oncology and Hematology, U.O.C. Hematology for Rare Blood and of Hematopoietic Organs Diseases, A.O. Reunited Hospitals Villa Sofia-Cervello , Palermo, Italy.
authors.forename: Alice
authors.initials: A
authors.lastname: Pecoraro
authors.affiliation: Department of Oncology and Hematology, U.O.C. Hematology for Rare Blood and of Hematopoietic Organs Diseases, A.O. Reunited Hospitals Villa Sofia-Cervello , Palermo, Italy.
authors.forename: Veronica
authors.initials: V
authors.lastname: Agrigento
authors.affiliation: Department of Oncology and Hematology, U.O.C. Hematology for Rare Blood and of Hematopoietic Organs Diseases, A.O. Reunited Hospitals Villa Sofia-Cervello , Palermo, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Troia
authors.affiliation: Department of Oncology and Hematology, U.O.C. Hematology for Rare Blood and of Hematopoietic Organs Diseases, A.O. Reunited Hospitals Villa Sofia-Cervello , Palermo, Italy.
authors.forename: Rosario
authors.initials: R
authors.lastname: Di Maggio
authors.affiliation: Department of Oncology and Hematology, U.O.C. Hematology for Rare Blood and of Hematopoietic Organs Diseases, A.O. Reunited Hospitals Villa Sofia-Cervello , Palermo, Italy.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Sacco
authors.affiliation: Department of Oncology and Hematology, U.O.C. Hematology for Rare Blood and of Hematopoietic Organs Diseases, A.O. Reunited Hospitals Villa Sofia-Cervello , Palermo, Italy.
authors.forename: Aurelio
authors.initials: A
authors.lastname: Maggio
authors.affiliation: Department of Oncology and Hematology, U.O.C. Hematology for Rare Blood and of Hematopoietic Organs Diseases, A.O. Reunited Hospitals Villa Sofia-Cervello , Palermo, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: D'Alcamo
authors.affiliation: Department of Oncology and Hematology, U.O.C. Hematology for Rare Blood and of Hematopoietic Organs Diseases, A.O. Reunited Hospitals Villa Sofia-Cervello , Palermo, Italy.
authors.forename: Rosalba
authors.initials: R
authors.lastname: Di Marzo
keywords: Genetic markers; Hemoglobinopathies; Hydroxyurea; Liquid erythroid cultures