Interleukin-3 receptor subunit alpha (CD123) (CD123)

Interleukin-3 receptor subunit alpha (CD123) is a type I transmembrane glycoprotein that serves as the primary ligand-binding component of the heterodimeric interleukin-3 (IL-3) receptor complex [2, 5]. It binds the cytokine IL-3 with high specificity and subsequently recruits the common beta subunit (CD131) to form a high-affinity signaling complex that activates the JAK-STAT, PI3K, and MAPK pathways [4, 8, 15]. These signaling cascades are essential for the proliferation, differentiation, and survival of hematopoietic progenitor cells and various immune cells [1, 19]. While CD123 is expressed at low levels on normal hematopoietic stem cells, it is significantly overexpressed in several hematologic malignancies, including acute myeloid leukemia (AML) and blastic plasmacytoid dendritic cell neoplasm (BPDCN) [9, 12, 15]. This differential expression makes CD123 a critical biomarker for identifying leukemic stem cells and an attractive target for therapeutic intervention [10, 14]. Current pharmacological approaches include the use of CD123-directed cytotoxins, such as the approved drug tagraxofusp, as well as antibody-drug conjugates, bispecific T-cell engagers, and chimeric antigen receptor (CAR) T-cell therapies [9, 16]. Therapeutic targeting of CD123 is associated with specific safety concerns, most notably capillary leak syndrome and cytokine release syndrome [15, 16].

Other names

CD123IL3RAIL-3R-alphaIL-3R subunit alphaInterleukin 3 receptor alpha (low affinity)hIL-3RaCD123 antigen

CD123-directed cytotoxin, antibody-drug conjugate (ADC), bispecific T-cell engager (BiTE/DART), chimeric antigen receptor (CAR) T-cell therapy, and neutralizing monoclonal antibody.