Circulating membrane vesicles in leukemic blood

Abstract

Ultramicroscopic membrane vesicles were found in the plasma of 17 patients with certain types of leukemia (acute promyelocytic leukemia, acute monocytic leukemia, acute myelomonocytic leukemia, and chronic myelogenous leukemia) and in guinea pigs with the L2C leukemia. Labeled vesicles were cleared from normal guinea pig plasma according to a two exponential function with a half-life for the second exponent of greater than 11 h. By immunofluorescence, vesicles shared antigens with the L2C leukemic cells. Attempts to elucidate the cellular origin of the circulating vesicles in human leukemias were less definitive. However, vesicles did not react with the platelet membrane antigen GP IIb/IIIa nor did the presence of circulating vesicles or vesicle-associated procoagulant activity correlate with the platelet count. In three patients studied serially, circulating vesicles paralleled disease activity. Vesicles were not detected in 16 other patients with leukemias including acute myelogenous leukemia and most lymphoid leukemias. Similarly, vesicles were not present in 29 normal plasmas or in 10 plasmas from patients with solid tumors or nonmalignant hematological disorders. In contrast to vesicles of similar appearance shed by a variety of solid and ascites tumor cells in vitro and in vivo, the vesicles circulating in leukemia patients and guinea pigs expressed variable and generally weak procoagulant activity and no tissue factor activity. Thus, although many of the patients with circulating vesicles expressed abnormal coagulation, we were not able to establish a close pathogenetic relationship between the procoagulant activity of circulating vesicles and clinical coagulopathies.