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 synthetase/RNase L system in malignancy, RNase L activity and an increased endoribonuclease activity were observed in peripheral blood mononuclear cell (PBMC) extracts from patients with chronic myelogenous leukemia. The cleavage of rRNA from intact ribosomes was used as the assay for both RNase L and the increased endoribonuclease activities. Novel rRNA cleavage products (NCP) were generated by extracts of Ficoll-purified mononuclear cells from chronic myelogenous leukemia (CML) patients and in the granulocytic fraction of both patients and healthy controls. Determination of the time course of rRNA degradation demonstrated that the novel cleavage products were rapidly derived from the further endoribonucleolytic degradation of the RNase L derived specific cleavage products. Prolonged incubation of mononuclear cell extracts from healthy controls also yielded the novel rRNA cleavage products. Comparisons of the kinetics of NCP production suggest that the novel endoribonuclease activity can be approximately 240-fold greater in PBMC extracts from CML patients than controls. Analysis of peripheral blood WBC count and differential indicated that the increased RNase activities 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 increased endoribonuclease activities may play a functional role in the biology of chronic myelogenous leukemia and may be important in the mechanism of action of interferon therapy in this disease.
Department of Neoplastic Diseases, Hahnemann University, Philadelphia, Pennsylvania 19102.
H R
HR
Hubbell
K
K
Kariko
R J
RJ
Suhadolnik
I
I
Brodsky
D004722:Endoribonucleases / Q000097:blood*; D006098:Granulocytes / Q000201:enzymology; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood* / Q000201:enzymology; D007958:Leukocyte Count; D007963:Leukocytes, Mononuclear / Q000201:enzymology*; D012335:RNA, Ribosomal / Q000378:metabolism; D012016:Reference Values
D012335:RNA, Ribosomal; D004722:Endoribonucleases; C031956:2-5A-dependent ribonuclease