Plasminogen activation in human acute leukaemias

Plasminogen activation is implicated in solid tumour growth, invasion and m etatastic spread. However, little is known about its role in leukaemia. We investigated the production by leukaemic cells of plasminogen activators [u rokinase (uPA )and tissue-type PA (tPA)], cell surface receptor for uPA (uP AR) and PA inhibitors (PAI-1 and PAI-2). Leukaemic cells from 37 patients [ 26 with acute myeloid leukaemia (AML) and 11 with acute lymphoid leukaemia (ALL)] were analysed for mRNA content and enzymatic activities. High levels of uPA mRNA were found in M1, M2, M3 and M4-M5 AMLs, whereas tPA mRNA was not detected in any of the analysed cases, uPAR mRNA was confined to subtyp es M4-M5. PAI-1 mRNA was detected in M3 and M4-M5. PAI-2 MRNA was found pre dominantly in M2 and M4-M5. SDS-PAGE/zymography analyses of cell extracts a nd supernatants after 24 and. 48 h of culture confirmed the production of a ctive uPA by AML cells (mainly M4-M5), but not by ALL. The finding of uPA, uPAR, PAI-I and PAI-2 synthesized by leukaemic cells suggests that plasmino gen activation may contribute to the invasive behaviour of these cells, the fibrinolytic imbalance observed in leukaemic patients and the differentiat ion and proliferation of M4-M5 by interaction of uPA with uPAR.