CD87 (urokinase-type plasminogen activator receptor), function and pathology in hematological disorders: a review

Abstract

The analysis of CD87 (urokinase-type plasminogen activator receptor -uPAR) expression has a potential role in the diagnostic or prognostic work-up of several hematological malignancies, particularly acute leukemia and multiple myeloma. The distribution of CD87 in acute myeloid leukemia (AML) varies according to the FAB subtype (highest expression in M5 and lowest in M0). Functionally, it is conceivable that the expression of CD87 could contribute to the invasive properties of the leukemic cells towards the skin and mucosal tissues as reflected by the clinical behavior of CD87 high cases. The lack of or weaker expression of CD87 on blast cells from ALL patients supports the concept that CD87 investigation might help in the distinction of AMLs from lymphoid malignancies. Among lymphoproliferative disorders, the expression of CD87 is exclusively found in pathological plasma cells. Since plasma cells also coexpress some adhesion molecules such as CD138 and CD56, this observation is consistent with the capacity of these cells to home in the bone compartment. High levels of soluble uPAR appear to represent an independent factor predicting worse prognosis and extramedullary involvement in multiple myeloma. Leukemia ( General aspectsThe urokinase-type plasminogen activator (uPA) system consists of a proteinase (the uPA), its receptor (the urokinase-type plasminogen activator receptor -uPAR or CD87) and two major inhibitors, the plasminogen activator inhibitor 1 (PAI 1) and PAI 2.

The Soluble Form of LR11 Protein Is a Regulator of Hypoxia-induced, Urokinase-type Plasminogen Activator Receptor (uPAR)-mediated Adhesion of Immature Hematological Cells

“…In fact, uPAR has been shown to be a major regulator of proliferation, marrow pool size, engraftment, and mobilization of murine HSPCs (17). Together with previous results of analyses of uPAR as a prognosis marker in leukemic patients (18), disturbed regulation of uPAR may be important in the pathogenesis of leukemias involving uPAR-expressing malignant cells. Although uPAR expression is known to be induced by hypoxia in cultured hematological cells (19), the mechanism underlying the up-regulation of uPAR under hypoxic conditions has not yet been elucidated.…”

Clinical Significance of CD87 Expression in Acute Myeloblastic Leukemia.

“…It may also explain the relationship between CD87 and the frequency of organomegaly. 1,7 A significant relationship between CD87 and organomegaly was also found (p< 0.05).…”

“…Cellular functions related to uPAR have multiple regulatory functions in cell migration, leucocyte adhesion, chemotaxis and signal conduction. [1][2][3][4] uPA and uPAR are expressed by leucocytes (neutrophil leucocytes, monocytes, macrophages, eosinophils, activated lymphocytes), endothelial cells and fibroblasts. Among the normal bone marrow cells uPAR is expressed on some myeloid precursors (promyelocytes, myelocytes, and metamyelocytes), monocytes, and their precursors but not on CD34(+) hematopoietic stem and progenitor cells.…”

“…Among the normal bone marrow cells uPAR is expressed on some myeloid precursors (promyelocytes, myelocytes, and metamyelocytes), monocytes, and their precursors but not on CD34(+) hematopoietic stem and progenitor cells. 1,5 Their functions in healthy cells include the conversion of plasminogen into plasmin, the extravasation associated with proteolytic breakdown of the adhesion molecules which are responsible from cell contact, the regulation of cytoskeletondependent events such as mobility and degranulation and increased bleeding tendency. [6][7][8][9][10] In clonal hematopoietic disorders, CD87 expression studies have focused on acute leukemias and multiple myeloma.…”

Role of flow cytometry in multiple myeloma and the prognostic significance of CD87 (uPAR) expression

“…Reports have suggested that malignant plasma cells expressed uPA and uPAR and that this active proteolytic system might have an effect on the bone marrow turnover in this disease. In addition, studies suggested that CD87 had a role in the pathogenesis of MM and was associated with the prognosis [7,8].…”