Homeostatic myeloid-biased cell expansion. In the human β-thalassemia trial, most of therapeutic effect results from a dominant myeloid-biased cell clone. In this clone, the HMGA2 integration site (IS) is present in similar proportions among erythroblasts, granulocyte, monocyte, and LTC-IC cells, but not in lymphocytes (LT); whereas its expression is strictly erythroid specific. Therefore, the HMGA2 IS-initiating cell is probably a myeloid-biased LT-HSC19/a cell with increased downstream cell production (1, in red) or a common myeloid progenitor with acquired self-renewal capability (2, in red). From Cavazzana-Calvo et al.³⁴