BCL11A is a transcriptional repressor that is crucial in brain and hematopoietic system development, as well as foetal-to-adult haemoglobin switching. In thalassemia, BCL11A inhibits y-globin expression and foetal haemoglobin in thyroid cells is it just in thyroid cells? Or is it rest of the body as well

Answer 1

BCL11A is not limited to thyroid cells; it has a broader role across different tissues in the body. In the context of thalassemia and other hemoglobinopathies, BCL11A functions to repress γ-globin expression and thus affects fetal hemoglobin (HbF) synthesis in erythroid cells, which are precursors to red blood cells. This repression occurs in hematopoietic systems, specifically within the bone marrow and other blood-forming tissues. By inhibiting γ-globin expression, BCL11A promotes the switch from fetal hemoglobin (which includes γ-globin) to adult hemoglobin (which includes β-globin).

This regulatory mechanism of BCL11A on hemoglobin switching is particularly significant for conditions like β-thalassemia and sickle cell disease, where reactivation of HbF production can ameliorate disease symptoms. Therefore, efforts to modulate BCL11A activity or expression as a therapeutic strategy aim to increase HbF levels throughout the body’s hematopoietic system, not just in the thyroid gland or thyroid cells.