RNASE-L AND INCREASED ENDORIBONUCLEASE ACTIVITIES IN THE MONONUCLEAR-CELLS OF PATIENTS WITH CHRONIC MYELOGENOUS LEUKEMIA

During investigations of the interferon-induced 2',5' oligoadenylate s ynthetase/RNase L system in malignancy, RNase L, activity and an incre ased endoribonuclease activity were observed in peripheral blood monon uclear cell (PBMC) extracts from patients with chronic myelogenous leu kemia. The cleavage of I RNA from intact ribosomes was used as the ass ay for both RNase L and the increased endoribonuclease activities. Nov el rRNA cleavage products (NCP) were gener ated by extracts of Ficoll- purified mononuclear cells from chronic myelogenous leukemia (CML) pat ients and in the granulocytic fraction of both patients and healthy co ntrols. Determination of the time course of I RNA degradation demonstr ated that the novel cleavage products were rapidly derived from the fu rther endoribonucleolytic degradation of the RNase L derived specific cleavage products. Prolonged incubation of mononuclear cell extracts f rom healthy controls also yielded the navel rRNA cleavage products. Co mparisons of the kinetics of NCP production suggest that the novel end oribonuclease activity can be approximately 240-fold greater in PBMC e xtracts from CML patients than controls. Analysis of peripheral blood WBC count and differential indicated that the increased RNase activiti es were associated with the presence of immature granulocytic cells in the peripheral blood (p = 0.001, Fisher's exact test). However, these activities were also found in the mononuclear cells of a CML patient in lymphoid blast crisis. Since CML is a stem cell disease, the novel endoribonuclease activity may be indicative of active disease, rather than a marker for immature granulocytes. Thus, the RNase L and increas ed endoribonuclease activities may play a functional role in the biolo gy of chronic myelogenous leukemia and may be important in the mechani sm of action of interferon therapy in this disease.