Hemoglobin subunit beta (HBB) T87Q variant (HBB(T87Q))

Hemoglobin subunit beta (HBB) T87Q variant is a transgenic protein produced in erythroid cells following the administration of gene therapies such as betibeglogene autotemcel or lovotibeglogene autotemcel. This specific variant contains a threonine-to-glutamine substitution at position 87, a modification designed to mimic the anti-sickling properties of fetal hemoglobin (HbF) and to allow for the distinct quantification of the transgenic protein from endogenous adult hemoglobin (Negre et al., 2015). In patients with beta-thalassemia, the HBB(T87Q) protein pairs with excess alpha-globin chains to form functional hemoglobin tetramers (HbA[T87Q]), restoring effective erythropoiesis and reducing transfusion dependence (Thompson et al., 2018). In patients with sickle cell disease, the T87Q mutation inhibits the polymerization of sickle hemoglobin (HbS), thereby reducing vaso-occlusive events and hemolysis (Kanter et al., 2022). The production of HBB(T87Q) is maintained long-term through the engraftment of genetically modified autologous hematopoietic stem cells (FDA Zynteglo Label, 2022; FDA Lyfgenia Label, 2023).

Other names

βA-T87Q-globinTransgenic beta-globinHbA(T87Q)Beta-globin T87QHBB T87QAT87Q-globin

The transgenic HBB(T87Q) protein combines with alpha-globin to form functional hemoglobin tetramers (HbA[T87Q]), which restore oxygen-carrying capacity in beta-thalassemia and inhibit the polymerization of sickle hemoglobin (HbS) in sickle cell disease (Thompson et al., 2018; Kanter et al., 2022).