Bleeding Tendency in Acute Promyelocytic Leukemia: Reversal by Cell Differentiation?

Abstract

Acute promyelocytic leukemia (APL) is a subvariety of acute myeloid leukemia (AML) and is associated with a high incidence of severe hemorrhage [7]. Tissue factor-like structures found on the leukemic blast cell, inducing disseminated intravascular coagulation (DIC), are often said to be responsible for this coagulopathy [2]. However, the observed bleeding disorder could not always be explained by DIC [5], and signs of fibrinolysis due to proteolytic lysosomal enzymes from the azurophilic granules were found [4]. Moreover, recently, specific fibrinolytic activity has also been described as a cause of the coagulopathy [6], and plasminogen activator has been found in the blast cells of patients with APL [3]. In a previous study [10] we investigated promyelocytic cell line cells (HL60) and blast cells from patients with APL and were able to show that in promyelocytes a combination of procoagulant activity (PCA) and proteolytic activity (lysosomal enzymes) exists that could be responsible for the observed bleeding tendency. Because HL60 cells are susceptible to differentiation in vitro to either more mature granulocytic or monocytic cells we are able to study whether combinations of PCA, proteolytic activity, and/or plasminogen activator activity exist in these cells, and whether these combinations are unique for the promyelocyte. We compared our findings with those obtained in blast cells of patients with different subtypes of AML.