Expression of CD25 fluctuates in the leukemia-initiating cell population of CD25-positive AML

CD25 is expressed on leukemic cells in 10–20% cases of acute myeloid leukemia (AML), and its expression is associated with poor prognosis. We reevaluated the relationship between CD25 expression and the leukemia-initiating cell (LIC) properties of AML using a patient-derived xenograft model. We divided lineage marker-negative (Lin(–)) CD34(+)CD38(–) or Lin(–)CD34(+) cells from CD25-positive AML into CD25-positive and -negative populations, and then transplanted each population into NOD.Cg-Prkdc(scid)Il2rg(tm1Wjl)/Sz mice. Leukemic engraftment was observed with both CD25-positive and -negative populations from three of nine CD25-positive AML patients. In two of those three patients, CD25-positive and -negative Lin(–)CD34(+) cells engrafted at the primary transplantation led to leukemic engraftment at the secondary transplantation, in which engrafted cells contained both CD25-positive and -negative Lin(–)CD34(+) AML cells. In an in vitro culture system, expression of CD25 was considerably induced in the CD25-negative population of Lin(–)CD34(+) cells from two cases of CD25-positive AML. In one case, CD25-positive Lin(–)CD34(+) cells gave rise to CD25-negative as well as -positive CD34(+) cells. These observations suggest that there exist CD25-positive and -negative populations that can reconstitute CD25-positive AML in a patient-derived xenograft model, and that CD25 expression fluctuates in the LICs of AML.