CD123, also known as the alpha chain of the interleukin-3 receptor (IL-3Rα), is a membrane-bound protein that plays a crucial role in immune regulation and hematopoiesis. It is overexpressed in various hematologic malignancies, including acute myeloid leukemia (AML), blastic plasmacytoid dendritic cell neoplasm (BPDCN), acute lymphoblastic leukemia (ALL), hairy cell leukemia, and systemic mastocytosis. The CD123 protein consists of three extracellular domains, a single-pass transmembrane domain, and a short intracellular region. It is involved in the growth, proliferation, survival, and differentiation of hematopoietic cells. CD123 is particularly significant as a biomarker for targeted therapy in these diseases, with various pharmacologic strategies and agents under investigation or already approved for clinical use. For instance, Tagraxofusp, an anti-CD123 antibody conjugated to diphtheria toxin, has been approved for use in patients with BPDCN.
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