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Suppression of the delayed rectifier type of voltage gated K+ outward
current in megakaryocytes from patients with myelogenous leukemias
L Kapural, MB Feinstein, F O'Rourke and A Fein
Department of Physiology, University of Connecticut Health Center,
Farmington 06030, USA.
In normal human megakaryocytes, we identified a delayed rectifier type of
voltage-gated outward K+ current (DRK). In two human megakaryoblastic tumor
cell lines (DAMI, CHRF-288-11) and the human erythroleukemia cell line
(HEL) the DRK current was not detected. To determine if the absence of the
DRK current in the tumor cells is the result of the underlying malignant
state, we examined megakaryocytes from myelogenous leukemia patients. In 24
of 29 megakaryocytes from the myelogenous leukemia patients, the DRK
current was greatly suppressed, whereas in the remaining 5 megakaryocytes a
normal large amplitude DRK current was present. We had the opportunity to
reexamine megakaryocytes from a patient with acute promyelocytic leukemia
(M3), after chemotherapy. Whereas the DRK current was suppressed before
treatment, the current reappeared after chemotherapy. Exposure to the
adenylate cyclase activator, forskolin, caused the appearance of a
voltage-gated outward current in the megakaryocytes of patients with acute
myelogenous leukemia. This finding suggests either that the channels
underlying the DRK current are present but somehow suppressed in
megakaryocytes from these patients or that forskolin induces a different
voltage-gated outward current. We suggest that the megakaryocytes from the
myelogenous leukemia patients with suppressed DRK current are abnormal,
whereas the others may be normal megakaryocytes. The suppression of the DRK
current may be a contributory factor to the dysregulation of thrombopoiesis
(Zittoun et al: Semin Hop Paris 44:183, 1968 and Rabellino et al: Blood
63:615, 1984) in myelogenous leukemias.
Volume 86,
Issue 3,
pp. 1043-1055,
08/01/1995
Copyright © 1995 by The American Society of Hematology

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