ReviewExpression of CD25 on leukemic stem cells in BCR-ABL1+ CML: Potential diagnostic value and functional implications

•CD25 is a novel STAT5-dependent marker of leukemic stem cells (LSCs) in CML.•In chronic phase CML, LSCs are usually CD25+/CD26+/IL-1RAP+.•CD25 is a functional regulator of LSC expansion and a potential target in CML.•The clinical value of CD25 as an LSC marker is being investigated.

Chronic myeloid leukemia (CML) is a stem cell-derived leukemia in which neoplastic cells exhibit the Philadelphia chromosome and the related oncoprotein BCR-ABL1. The disease is characterized by an accumulation of myeloid precursor cells in the peripheral blood and bone marrow (BM). A small fraction of neoplastic cells in the CML clone supposedly exhibits self-renewal and thus long-term disease-propagating ability. However, so far, little is known about the phenotype, function, and target expression profiles of these leukemic stem cells (LSCs). Recent data suggest that CML LSCs aberrantly express the interleukin-2 receptor alpha chain CD25. Whereas normal CD34+/CD38− BM stem cells display only low amounts of CD25 or lack CD25 altogether, CD34+/CD38− LSCs express CD25 strongly in more than 90% of all patients with untreated CML. As a result, CD25 can be used to identify and quantify CML LSCs. In addition, it has been shown that CD25 serves as a negative growth regulator of CML LSCs. Here, we review the value of CD25 as a novel marker and potential drug target in CML LSCs.