Figure 4.

Combination therapy using lentiviral-vector-derived β-globin expression and chemical γ-globin induction.

Notes: Combination of gene therapy and HbF induction leads to high production of both HbA and HbF and reduction of excess α-globin chains, as shown for representative experiments performed with erythroid precursor cells from (A) a β⁰-thalassemia patient homozygous for the codon-39 stop codon mutation (genotype β⁰39/β⁰39) and (B) a β⁰39/β+IVSI−110-thalassemia patient. Cells were cultured without treatment (-) and in the presence of T9W, mithramycin (MTH), and T9W with MTH, respectively, as indicated. The % of HbF (white boxes), HbA (black boxes), and α-globin peak (gray boxes) is shown (Zuccato et al, unpublished data, 2014; and data from Zuccato C, Breda L, Salvatori F, et al. A combined approach for β-thalassemia based on gene therapy-mediated adult hemoglobin (HbA) production and fetal hemoglobin (HbF) induction. Ann Hematol. 2012;91:1201–1213.)¹¹⁴