Myeloid leukaemic cells can lyse fibrin directly

Purified preparations of circulating leukaemic blast cells from patients with acute myeloid (M1-7) or acute lymphoblastic leukaemia, and the myeloid or lymphoid cells from patients with chronic myeloid or lymphocytic forms of leukaemia, were incorporated into clots prepared from fibrinogen and plasminogen. Patterns of lysis were followed and measured by light transmission in a microtitre plate reader. Mature polymorphonuclear and mononuclear cell fractions from normal individuals were studied concurrently for comparison. Blast cells from the myeloid forms of acute leukaemia (M2-4) and 'myeloid' cell fractions from patients with chronic myeloid leukaemia were capable of lysing plasminogen-containing clots; this activity was neutralized by addition of immunoglobulin against urokinase plasminogen activator (u-PA), but not by anti-tissue plasmogen activator (t-PA). Mature polymorphonuclear and mononuclear cells from normal individuals lacked lytic activity, as did the leukaemic cells from patients with acute lymphoblastic or chronic lymphocytic leukaemia. Lysed blast cells showed the presence of free plasminogen activator on sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) with overlay zymography, also neutralized by anti-u-PA, whereas normal polymorphonuclear and mononuclear cells did not. These observations suggest that mechanisms underlying some forms of severe bleeding in acute myeloid leukaemias have a critical fibrinolytic component generated by the blast cells themselves.