Differential expression of growth differentiation factor 11 and growth differentiation factor 15 and their association with iron overload in β-thalassemia patients undergoing fetal hemoglobin induction or transfusion therapy

BACKGROUND: Beta-thalassemia is a common inherited hemoglobin disorder characterized by defective β-globin synthesis, resulting in globin chain imbalance, ineffective erythropoiesis (IE), chronic hemolysis, and iron dysregulation. Growth differentiation factors (GDF-11 and GDF-15) are implicated in erythroid maturation and iron metabolism, but their expression across different treatment strategies remains insufficiently defined. OBJECTIVES: To evaluate the expression of GDF-11 and GDF-15 in β-thalassemia patients receiving fetal hemoglobin (HbF) inducers or regular transfusions and to assess their association with serum ferritin. MATERIALS AND METHODS: This cross-sectional study included 173 β-thalassemia patients receiving HbF inducers ( n = 140; 80.92%) or regular transfusions ( n = 33; 19.08%), and 27 healthy controls (HCs). Serum ferritin levels were recorded, and relative mRNA expression of GDF-11 and GDF-15 was quantified using real-time polymerase chain reaction. The association of GDF-11 and GDF-15 expression levels with serum ferritin was evaluated using linear regression analysis. RESULTS: Both GDF-11 and GDF-15 expression levels were significantly elevated in β-thalassemia patients compared with HCs. Median GDF-11 expression levels were 2.20-fold in HCs, 9.56-fold in transfusion-dependent patients, and 7.92-fold in patients receiving HbF inducers, while median GDF-15 expression levels were 2.86-fold, 6.86-fold, and 9.96-fold, respectively. GDF-11 expression was significantly higher in transfusion-dependent patients than in the HbF group ( P = 0.011), whereas GDF-15 expression was significantly higher in the HbF group ( P = 0.0368). No significant correlation was observed between either GDF-11 or GDF-15 expression and serum ferritin levels. CONCLUSIONS: Elevated GDF-11 and GDF-15 expression support their association with IE in β-thalassemia. Differential expression across treatment groups suggests treatment-related modulation of erythroid regulatory pathways; however, no independent association with iron burden was identified.