Hemostatic balance on the surface of leukemic cells: the role of tissue factor and urokinase plasminogen activator receptor.
OBJECTIVE
The frequency of thrombotic complications is increased in patients with acute leukemia. Since coagulation processes take place on cell membranes, we hypothesized that expression of coagulation proteins on blast membrane could determine the hemostatic balance on the surface of leukemic cells and may correlate with thrombotic manifestations.


METHODS
Fifty-one consecutive patients with newly diagnosed acute leukemia were enrolled over an 11-month period. Twenty-five of the patients had acute myeloid leukemia (AML)-M(0-2), 11 had AML-M3, 6 had AML-M(4-5), and 9 acute lymphocytic leukemia (ALL). Peripheral blood and bone marrow were analyzed by flow-cytometry for tissue factor, protease-activated receptor 1, tissue factor pathway inhibitor, urokinase plasminogen activator receptor, and thrombomodulin.


RESULTS
Regardless of the leukemia subtype, tissue factor was predominantly present on leukemic blast surfaces as compared to protease-activated receptor 1, tissue factor pathway inhibitor, urokinase plasminogen activator receptor and thrombomodulin and it was significantly elevated (mean 63+/-6%) in AML-M3 and AML-M(4-5) as compared to AML-M0(-2) and ALL (mean 37+/-4%, p<0.001). Likewise, urokinase plasminogen activator receptor expression was greater in AML-M(4-5) (49+/-11%) than in in AML- M(0-2), M3 and, ALL (mean 17+/-3%, p<0.001). Thrombotic manifestations were present in 13 out of 51 (26%) patients. The tissue factor to urokinase plasminogen activator receptor ratio was higher in patients with a thrombotic event than in patients without thrombotic events (16+/-4 vs. 6+/-2, p=0.042).


CONCLUSIONS
This study demonstrates that tissue factor predominates on leukemic blast surface, particularly in M3 and M4-5 subtypes, while urokinase plasminogen activator receptor is increased on M4-5 blasts. The hemostatic balance on the blast surface may contribute to thrombotic manifestations in leukemic patients.
Nadir
Yona
Y
Department of Hematology and Bone Marrow Transplantation, Rambam Medical Center, Haifa, Israel. ynadir@netvision.net.il
Katz
Tamar
T
Sarig
Galit
G
Hoffman
Ron
R
Oliven
Anna
A
Rowe
Jacob M
JM
Brenner
Benjamin
B
D000328:Adult; D000368:Aged; D002462:Cell Membrane / Q000502:physiology; D005260:Female; D006487:Hemostasis / Q000502:physiology*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism* / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D011956:Receptors, Cell Surface / Q000502:physiology*; D055293:Receptors, Urokinase Plasminogen Activator; D013925:Thromboplastin / Q000502:physiology*; D013927:Thrombosis / Q000378:metabolism* / Q000503:physiopathology*
C524898:PLAUR protein, human; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D013925:Thromboplastin