In APL cells, annexin II (ANXII) levels are abnormally high and have been considered responsible for the increased production of plasmin (Pl). In fact, ANXII is a receptor for both tissue plasminogen activator (tPA) and plasminogen (Plg). The close position of tPA to Plg favors the activation of Plg to Pl, the most important fibrinolytic enzyme responsible for the observed fibrinolysis in APL (A). Supplementation of methionine increases the levels of homocysteinemia (Hcy), producing hyperhomocysteinemia that inhibits the binding of tPA to ANXII, therefore reverting hyperfibrinolysis because tPA can no longer activate Plg to Pl (B). A lack of activation of Plg by tPA is also produced by the infusion, in leukemic mice, of the hexapeptide LCKLSL because tPA fails to link to the hexapeptide LCKLSL present in the molecule of ANXII (C).