SUPPRESSION OF THE DELAYED RECTIFIER TYPE OF VOLTAGE-GATED K+ OUTWARDCURRENT IN MEGAKARYOCYTES FROM PATIENTS WITH MYELOGENOUS LEUKEMIAS

In normal human megakaryocytes, we identified a delayed rectifier type of voltage-gated outward K+ current (DR(K)). In two human megakaryobl astic tumor cell lines (DAMI, CHRF-288-11) and the human erythroleukem ia cell line (HEL) the DR(K) current was not detected, To determine if the absence of the DR(K) current in the tumor cells is the result of the underlying malignant state, we examined megakaryocytes from myelog enous leukemia patients, In 24 of 29 megakaryocytes from the myelogeno us leukemia patients, the DR(K) current was greatly suppressed, wherea s in the remaining 5 megakaryocytes a normal large amplitude DR(K) cur rent was present. We had the opportunity to reexamine megakaryocytes f rom a patient with acute promyelocytic leukemia (M3), after chemothera py. Whereas the DR(K) current was suppressed before treatment, the cur rent 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 leuk emia, This finding suggests either that the channels underlying the DR (K) current are present but somehow suppressed in megakaryocytes from these patients or that forskolin induces a different voltage-gated out ward current. We suggest that the megakaryocytes from the myelogenous leukemia patients with suppressed DR(K) current are abnormal, whereas the others may be normal megakaryocytes. The suppression of the DR(K) current may be a contributory factor to the dysregulation of thrombopo iesis (Zittoun et al: Semin Hop Paris 44:183, 1968 and Rabellino et al : Blood 63:615, 1984) in myelogenous leukemias. (C) 1995 by The Americ an Society of Hematology.