CD123 is the alpha chain of interleukin 3 receptor (IL-3R alpha). This subunit heterodimerizes with the interleukin 3 receptor beta chain (CD131), which is shared with other receptors. CD123 interacts with IL-3 specifically, but with low affinity, and association with the beta subunit confers high affinity binding to the receptor heterodimer. Both chains are required for signaling, but receptor activation and signal transduction depend on IL-3 binding to CD123 as the initial step.
High CD123 expression is detected in various hematological malignancies, especially in case of both acute and chronic myeloid leukemia, adult and childhood B-cell acute lymphoblastic leukemia, chronic lymphocytic leukemia, Hodgkin lymphoma, hairy cell leukemia, blastic plasmacytoid dendritic cells neoplasm, systemic mastocytosis and myelodysplastic syndrome. Lower expression can be detected in T-cell acute lymphoblastic leukemia, and in naturally CD123-expressing hematopoietic cells, plasmacytoid dendritic cells and endothelial cells.
CD123 is highly expressed on leukemic stem cells and serves as a marker to distinguish them from normal hematopoietic stem cells, and it is also expressed on more differentiated leukemic blasts. Hence it is being used for immunotherapy, mainly in case of AML, B-ALL, and BPDCN. Differences in antigen densities between leukemic and healthy cells are important for optimal therapeutic window. CD123 expression positively correlates with minimal residual disease after treatment and can be used as a marker of treatment success and a prognostic factor.
Fig. 1: Schematic image of CD123 as a biomarker.
The mouse monoclonal antibody 6H6 recognizes an extracellular epitope of human CD123.
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Fig. 2: Flow cytometry analysis (surface staining) of human peripheral blood with anti-CD123 (6H6) PE-Cy™7.
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