Interleukin-3 receptor (IL-3 R) is a heterodimeric structure composed of a 70 kDa IL-3 R alpha subunit (IL-3 Rα or CD123) and a 120-140 kDa IL-3 R beta subunit (IL-3 Rβ or CD131). IL-3Rα is a glycoprotein member of the hematopoietic receptor superfamily. IL-3 Rα binds IL-3 with relatively low affinity. In the presence of IL-3 Rβ, however, IL-3 R alpha has a much higher affinity for IL-3.Emerging studies demonstrate that CD123, the IL-3 Rα, is highly expressed in leukemic stem cells (LSCs), while not normal hematopoietic stem cells (HSCs), and associates with treatment response, minimal residual disease (MRD) detection and prognosis. Furthermore, CD123 is an important marker for the identification and targeting of LSCs for refractory or relapsed leukemia.