Interleukin-3 receptor (IL-3R) (IL-3R)

The Interleukin-3 receptor (IL-3R) is a high-affinity heterodimeric complex composed of a cytokine-specific alpha subunit (IL-3RA or CD123) and a common beta subunit (CSF2RB or CD131) shared with the IL-5 and GM-CSF receptors [1, 2]. This receptor complex is primarily expressed on hematopoietic progenitor cells, where it mediates the biological effects of IL-3, including the stimulation of cell proliferation, differentiation, and survival through the activation of the JAK2/STAT5, MAPK, and PI3K/Akt signaling pathways [4, 5]. In pathological contexts, the alpha subunit (CD123) is frequently overexpressed on the surface of malignant cells in hematologic disorders such as acute myeloid leukemia (AML) and blastic plasmacytoid dendritic cell neoplasm (BPDCN), while remaining low or absent on normal hematopoietic stem cells [13]. This differential expression pattern has established the IL-3 receptor as a significant therapeutic target. Current clinical strategies include the use of targeted toxins like tagraxofusp, antibody-drug conjugates such as pivekimab sunirine, and various bispecific antibodies and CAR-T cell therapies designed to selectively eliminate CD123-positive leukemic cells [2, 13].

Other names

CD123CD131IL3RACSF2RBIL-3 receptor alpha / common beta chain complexHigh-affinity interleukin-3 receptorInterleukin-3 receptor subunit alphaCytokine receptor common subunit betabeta-cCommon beta subunit

Targeted toxin, antibody-drug conjugate, bispecific T-cell engager, and antibody-dependent cellular cytotoxicity targeting the CD123 subunit.