Comparison of changes in blood cells and hemostatic biomarkers in mouse xenograft models of acute myeloid leukemia and acute promyelocytic leukemia.

BACKGROUND

Leukemia patients have an increased risk of both thrombosis and bleeding due to a dysregulated hemostatic system. Levels of coagulation and fibrinolysis activation markers are increased, whereas levels of platelets and fibrinogen are decreased in leukemia patients. Mouse models can be used to study the pathways that contribute to coagulopathy in leukemia.

OBJECTIVES

To measure blood cells and hemostatic biomarkers in a mouse xenograft model of acute myeloid leukemia (AML) and compare them with a mouse xenograft model of acute promyelocytic leukemia (APL).

METHODS

We established a mouse xenograft model of AML by injecting HL-60-Luc2 cells into NOD.Cg-Prkdc scid Il2rg tm1Wjl /SzJ mice and monitored the growth of leukemic cells by measuring luciferase expression. Levels of blood cells and hemostatic biomarkers were measured in leukemic mice. The parameters of the AML model were compared with those of the APL model using NB4-Luc cells.

RESULTS

AML mice exhibited an increase in white blood cells, an increase in a marker of coagulation activation (thrombin-antithrombin complexes), an increase in a marker of fibrinolysis activation (plasmin-antiplasmin complexes), and a decrease in platelets and fibrinogen compared with control mice. No increase in white blood cell counts was observed in APL mice. APL mice had significantly higher levels of thrombin-antithrombin complexes compared with AML mice.

CONCLUSION

These leukemia mouse models can be used to understand how the hemostatic system is dysregulated in leukemia.