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Recent studies indicate that abnormalities of the alpha-chain of the interleukin-3 receptor (IL-3RA or CD123) are frequently observed in some leukemic disorders and may contribute to the proliferative advantage of leukemic cells. This review analyzes the studies indicating that CD123 is overexpressed in various hematologic malignancies, including a part of acute myeloid and B-lymphoid leukemias, blastic plasmocytoid dendritic neoplasms (BPDCN) and hairy cell leukemia.  Given the low/absent CD123 expression on normal hematopoietic stem cells, attempts have been made at preclinical first, and then at clinical level to target this receptor. Since the IL-3R is a membrane receptor there are two relatively simple means to target this molecule, either using its natural ligand or neutralizing monoclonal antibodies. Recent reports using a fusion molecule composed by human IL-3 coupled to a truncated diphteria toxin have shown promising antitumor activity in BPDCN and AML patients.

CD 123 is a membrane biomarker and a therapeutic target in hematologic malignancies