CD123 and CD33
In hematological malignancies, such as AML, CD123 as well as CD33 have been described as the “classical” CSC markers (492, 493). CD123 is a marker expressed on LSCs (395, 397, 494), but not exclusively (395, 398). In AML patients, CD123 expression correlates to the therapy response rate (413, 495), the relapse risk (403), and a shorter disease-free period and OS (399, 413). CD123 has been associated with increased proliferation and differentiation (494, 496).
CD33 is historically, the most commonly used marker for AML stem cells, with clinical implementation of CD33 targeting, dating back to the Food and Drug Administration (FDA) approval of gemtuzumab ozogamicin (GO) in 2000 (497). CD33 is highly expressed on blasts in around 85–90% of AML patients (433, 438, 497) and also expressed at higher densities in CML (433, 438) but less on healthy hematopoietic stem cells (HSCs). These cells are additionally characterized by expression of CD25, CD26, and Interleukin-1 receptor accessory protein (IL-1RAP) and also other markers (440).