Interleukin-3 receptor subunit alpha (IL3RA) (IL3RA)

Interleukin-3 receptor subunit alpha (IL3RA), also known as CD123, is a type I transmembrane protein that functions as the primary binding component of the high-affinity interleukin-3 (IL-3) receptor complex [1][3]. It is predominantly expressed on hematopoietic progenitor cells and plays a critical role in regulating cell proliferation, survival, and differentiation through the activation of the JAK/STAT and PI3K/mTOR signaling pathways [2][4]. In various hematologic malignancies, such as blastic plasmacytoid dendritic cell neoplasm (BPDCN) and acute myeloid leukemia (AML), IL3RA is significantly overexpressed, making it a valuable therapeutic target [3][7]. Drugs like tagraxofusp exploit this by fusing IL-3 to a truncated diphtheria toxin; upon binding to IL3RA and internalization, the toxin's catalytic domain enters the cytosol and inactivates eukaryotic elongation factor 2 (EF-2) via ADP-ribosylation [2][6]. This mechanism effectively halts protein synthesis and induces apoptosis in the malignant cell [7][8]. Other therapeutic strategies targeting this axis include monoclonal antibodies, antibody-drug conjugates, and CAR-T cell therapies designed to eliminate CD123-positive cancer cells while sparing normal tissues with lower receptor density [5][9].

Other names

CD123IL-3RAInterleukin-3 receptor alpha chainCD123 antigenhIL-3Ra

Binding to the IL3RA (CD123) receptor followed by receptor-mediated endocytosis and subsequent inactivation of Eukaryotic Elongation Factor 2 (EF-2) via ADP-ribosylation (in the case of immunotoxins like tagraxofusp), or induction of antibody-dependent cellular cytotoxicity (ADCC) and inhibition of IL-3 signaling.