Quantification of HBG mRNA in primary erythroid cultures: prediction of the response to hydroxyurea in sickle cell and beta-thalassemia

Background and Objective Increased expression of fetal hemoglobin (HbF) may ameliorate the clinical course of hemoglobinopathies like sickle cell disease (SCD) and β‐thalassemia. Hydroxyurea (HU) can stimulate HbF production in these diseases but the response is highly variable indicating the utilit...

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Bibliographic Details
Published in:European journal of haematology 2014-01, Vol.92 (1), p.66-72
Main Authors: Pecoraro, Alice, Rigano, Paolo, Troia, Antonio, Calzolari, Roberta, Scazzone, Concetta, Maggio, Aurelio, Steinberg, Martin H., Marzo, Rosalba Di
Format: Article
Language:English
Subjects:
Adult
Aged
Anemia, Sickle Cell - blood
Anemia, Sickle Cell - drug therapy
Anemia, Sickle Cell - genetics
beta-Thalassemia - blood
beta-Thalassemia - drug therapy
beta-Thalassemia - genetics
Erythroid Precursor Cells - metabolism
Female
Fetal Hemoglobin - genetics
gamma-Globins - genetics
Gene Expression
Humans
hydroxyurea
Hydroxyurea - administration & dosage
Hydroxyurea - therapeutic use
liquid erythroid cultures
Male
Middle Aged
Primary Cell Culture
real-time quantitative PCR
RNA, Messenger - genetics
sickle cell disease
Treatment Outcome
Young Adult
β-thalassemia
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Summary:Background and Objective Increased expression of fetal hemoglobin (HbF) may ameliorate the clinical course of hemoglobinopathies like sickle cell disease (SCD) and β‐thalassemia. Hydroxyurea (HU) can stimulate HbF production in these diseases but the response is highly variable indicating the utility of developing an in vitro test to predict the patient's response to HU. We assessed whether the HbF response of patients with SCD and thalassemia intermedia (TI) to HU correlates with HBG (both γ‐globin genes) expression in their cultured erythroid progenitors following exposure to HU. Patients and Methods We exposed primary erythroid cultures from peripheral blood mononuclear cells from 30 patients with SCD and 15 with TI to HU and measured HBG mRNA by real‐time quantitative PCR. The same patients were then treated with HU and their HbF response after treatment with a stable dose of HU was compared with the mRNA results in cultured cells. Results and Conclusion The fold increase in HBG mRNA in erythroid progenitors was similar to the fold increase in HbF in vivo. Quantification of HBG mRNA in erythroid progenitor cell cultures from patients with SCD and TI is predictive of their clinical response to HU.
ISSN:0902-4441
1600-0609
DOI:10.1111/ejh.12204