Myeloid leukaemic cells can lyse fibrin directly

Purified preparations of circulating leukaemic blast cells from patients wi th acute myeloid (M1-7) or acute lymphoblastic leukaemia, and the myeloid o r lymphoid cells from patients with chronic myeloid or lymphocytic forms of leukaemia, were incorporated into clots prepared from fibrinogen and plasm inogen. 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 ad dition of immunoglobulin against urokinase plasminogen activator (u-PA), bu t not by anti-tissue plasmogen activator (t-PA). Mature polymorphonuclear a nd mononuclear cells from normal individuals lacked lytic activity, as did the leukaemic cells from patients with acute lymphoblastic or chronic lymph ocytic leukaemia. Lysed blast cells showed the presence of free plasminogen activator on sodium dodecyl sulphate polyacrylamide gel electrophoresis (S DS-PAGE) with overlay zymography, also neutralized by anti-u-PA, whereas no rmal polymorphonuclear and mononuclear cells did not. These observations su ggest that mechanisms underlying some forms of severe bleeding in acute mye loid leukaemias have a critical fibrinolytic component generated by the bla st cells themselves.