Preferential expression of double-stranded ribonucleic acid in tumor versus normal cells: Biological and clinical implications

In an effort to develop a new tumor marker suitable for flow cytometric analysis, we examined the value of double-stranded ribonucleic acid (ds-RNA) measurements using propidium iodide after DN'ase treatment. Cellular ds-RNA content was evaluated both in experimental cell lines and in clinical specimens. Higher levels of ds-RNA were present in tumor cells as compared with normal cells. In tumor cells, fluorescence was intensely localized in the nucleolus and was more diffuse in the cytoplasm. Change of <10% in the ds-RNA levels was observed in cell lines as a function of cytokinetic determinants such as cycle phase, culture age, and cycle traverse rate. Tumor differentiation by dimethylsulfoxide resulted in a significant decrease in cellular ds-RNA content. For quantitative comparison of clinical material, a ds-RNA excess was defined in relationship to normal peripheral blood lymphocytes. ds-RNA excess >30% was observed in only one of 34 normal tissues (3%) as compared with 124 of 201 neoplastic tissue samples (62%). This incidence was higher in patients with acute leukemia (76%), high-grade and intermediate-grade lymphoma (75%), and high tumor stage myeloma (83%), as compared with chronic leukemia (20%), low-grade lymphoma (25%), and intermediate or low tumor mass myeloma (43%). Prognostically, a high pretreatment ds-RNA excess in myeloma was associated with a lower remission rate. The persistence of ds-RNA excess in the bone marrow of patients with acute myelogenous leukemia in remission predicted for a shorter remission duration (seven v 22 months; P = .05). We conclude that ds-RNA excess, as readily measured objectively and quantitatively by flow cytometry, may have important diagnostic and prognostic implications for the management of patients with malignant disease.