Combined procoagulant activity and proteolytic activity of acute
promyelocytic leukemic cells: reversal of the bleeding disorder by cell
differentiation
PW Wijermans, VI Rebel, GJ Ossenkoppele, PC Huijgens and MM Langenhuijsen
Free University Hospital, Department of Haematology, Amsterdam, The
Netherlands.
In the human promyelocytic cell line HL60, we observed both a strong
procoagulant activity (PCA) on the cell membrane and proteolytic activity
in the lysate of these cells. Because these cell-line cells are susceptible
to differentiation to either a more mature granulocytic or monocytic form,
we were able to study the hypothesis that the combination of PCA and
proteolytic activity is confined to the promyelocyte. This may explain the
severe coagulopathy seen in patients with acute promyelocytic leukemia.
Cell differentiation in a myeloid direction induced by retinoic acid or
DMSO led to a diminished PCA, while not affecting the fibrinolytic
activity. On the other hand, monocytic differentiation obtained by
culturing the cells in the presence of 1; 25 dihydroxy vitamin D3 led to
the complete disappearance of the proteolytic activity of the cell lysate,
although the procoagulant activity was still present. Furthermore, we found
that the elastase activity almost disappeared after monocytic
differentiation. We also studied the PCA, proteolytic activity, and
elastase activity of blast cells of patients with acute myeloid leukemia.
Only in patients with acute promyelocytic leukemia did we observe both a
strong PCA and fibrinolytic activity. This supports our hypothesis that the
combination of these activities is unique to the promyelocyte and may
explain the observed bleeding complications in patients with acute
promyelocytic leukemia.
Volume 73,
Issue 3,
pp. 800-805,
02/15/1989
Copyright © 1989 by The American Society of Hematology
