Preferential expression of double-stranded ribonucleic acid in tumor versus
normal cells: biological and clinical implications
HM Kantarjian, B Barlogie, M Pershouse, D Swartzendruber, MJ Keating, KB McCredie and EJ Freireich
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
less than 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 greater
than 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.
Volume 66,
Issue 1,
pp. 39-46,
07/01/1985
Copyright © 1985 by The American Society of Hematology
