High expression of urokinase plasminogen activator receptor (UPA‐R) in acute myeloid leukemia (AML) is associated with worse prognosis

Urokinase‐type plasminogen activator receptor (UPA‐R; CD87) is a membrane protein responsible for plasmin expression on cells facilitating cellular extravasations and tissue invasions. We studied the expression of the UPA‐R on bone marrow (BM) cells of 93 patients with acute myeloid leukemia at first diagnosis and 8 healthy probands as controls by FACS analysis using phycoerythrin (PE)‐conjugated antibodies. A case was defined as UPA‐R‐positive (UPA‐R+) if >20% of the gated cells expressed UPA‐R. Whereas none of the 8 healthy BM samples was positive for the UPA‐R, 32 (34%) of the 93 AML samples were UPA‐R+. Expression of UPA‐R was heterogeneous in different FAB types, however, with the highest expression rates in monocytic subtypes (FAB M4/M5): 18%/19%/30% of UPA‐R+ cases were found in M1/M2 or M3, and 58%/80% of cases with M4 or M5 were UPA‐R+. Proportions of UPA‐R+ cells varied between 1% and 98% of the mononuclear cell fractions, with the highest proportions in M4/M5 subtypes (on average 27%/40% UPA‐R+ cells) and the lowest expression in AML M2 (11% UPA‐R+ cells). The density of expressed UPA‐R, estimated as mean channel fluorescence activity, was highest in cases with AML M1 (mFI: 124) followed by M4 and M5 (mFI: 78/77) and lowest in AML M2 (mFI: 43). In sAML, higher proportions of UPA‐R+ cases (8 of 18; 44%) compared to pAML (24 of 75; 32%) were found as well as higher proportions of UPA‐R+ cells (27% vs. 19%). Separating our patients' cohort in cytogenetic risk groups, we could not detect significant differences in the UPA‐R expression profiles. For evaluations of the clinical course of AML, only patients treated by the AML‐CG protocol (n = 65) were included. In the group of patients who did not respond to AML‐CG therapy, significantly higher proportions of UPA‐R+ cells (31% vs. 14%, P = 0.0015, t‐test) were found. By evaluating a cut‐off value for the percentage of positive cells that allows the most significant separation and differentiation between cases with shorter or longer relapse‐free survival times, we could show that patients with >26.5% UPA‐R‐positive cells were characterized by a significantly higher risk for relapse compared to cases with