Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1974 Apr;71(4):1309–1313. doi: 10.1073/pnas.71.4.1309

Relationship Between RNA-directed DNA Polymerase (Reverse Transcriptase) from Human Acute Leukemic Blood Cells and Primate Type-C Viruses

R E Gallagher *, G J Todaro †, R G Smith *, D M Livingston †,‡, R C Gallo *
PMCID: PMC388216  PMID: 4133850

Abstract

An RNA-directed DNA polymerase was isolated from the peripheral blood leukocytes of a patient with acute myelomonocytic leukemia by successive purification of a particulate cytoplasmic fraction with endogenous, ribonuclease-sensitive DNA polymerase activity. Like RNA-directed DNA polymerase from mammalian type-C virus, the human leukemic cell enzyme efficiently utilized (A)n·(dT)12-18 and (C)n·(dG)12-18 and had an approximate molecular weight of 70,000. Further, the leukemic cell enzyme was strongly inhibited by antisera to RNA-directed DNA polymerase of primate type-C virus in a fashion similar to that noted with an extensively purified RNA-directed DNA polymerase from a person with acute myelogenous leukemia [Todaro, G.J. & Gallo, R.C. (1973), Nature 244, 206]. By these biochemical and immunological results the leukemic cell enzyme could be differentiated from all other known cellular DNA polymerases but could not be distinguished from RNA-directed DNA polymerase of primate type-C virus. We interpret these data, combined with observations published elsewhere, to indicate that human acute myelogenous leukemia cells contain components related to primate type-C virus. The parameters used in this study may provide the specificity and sensitivity required for determining the presence or absence and (if present) the relatedness of RNA-directed DNA polymerase in other cases and types of human leukemia.

Keywords: human leukemia, antibody to virus polymerase

Full text

PDF
1311

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abrell J. W., Gallo R. C. Purification, characterization, and comparison of the DNA polymerases from two primate RNA tumor viruses. J Virol. 1973 Sep;12(3):431–439. doi: 10.1128/jvi.12.3.431-439.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Baltimore D., Smoler D. Primer requirement and template specificity of the DNA polymerase of RNA tumor viruses. Proc Natl Acad Sci U S A. 1971 Jul;68(7):1507–1511. doi: 10.1073/pnas.68.7.1507. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Baxt W., Hehlmann R., Spiegelman S. Human leukaemic cells contain reverse transcriptase associated with a high molecular weight virus-related RNA. Nat New Biol. 1972 Nov 15;240(98):72–75. doi: 10.1038/newbio240072a0. [DOI] [PubMed] [Google Scholar]
  4. Bhattacharyya J., Xuma M., Reitz M., Sarin P. S., Gallo R. C. Utilization of mammalian 70S RNA by a purified reverse transcriptase from human myelocytic leukemic cells. Biochem Biophys Res Commun. 1973 Sep 5;54(1):324–334. doi: 10.1016/0006-291x(73)90926-1. [DOI] [PubMed] [Google Scholar]
  5. Bolden A., Fry M., Muller R., Citarella R., Weissbach A. The presence of a polyriboadenylic acid-dependent DNA polymerase in eukaryotic cells. Arch Biochem Biophys. 1972 Nov;153(1):26–33. doi: 10.1016/0003-9861(72)90416-x. [DOI] [PubMed] [Google Scholar]
  6. Fridlender B., Fry M., Bolden A., Weissbach A. A new synthetic RNA-dependent DNA polymerase from human tissue culture cells (HeLa-fibroblast-synthetic oligonucleotides-template-purified enzymes). Proc Natl Acad Sci U S A. 1972 Feb;69(2):452–455. doi: 10.1073/pnas.69.2.452. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Gallo R. C., Miller N. R., Saxinger W. C., Gillespie D. Primate RNA tumor virus-like DNA synthesized endogenously by RNA-dependent DNA polymerase in virus-like particles from fresh human acute leukemic blood cells. Proc Natl Acad Sci U S A. 1973 Nov;70(11):3219–3224. doi: 10.1073/pnas.70.11.3219. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hardy W. D., Jr, Old L. J., Hess P. W., Essex M., Cotter S. Horizontal transmission of feline leukaemia virus. Nature. 1973 Aug 3;244(5414):266–269. doi: 10.1038/244266a0. [DOI] [PubMed] [Google Scholar]
  9. Kato K. I., Gonçalves J. M., Houts G. E., Bollum F. J. Deoxynucleotide-polymerizing enzymes of calf thymus gland. II. Properties of the terminal deoxynucleotidyltransferase. J Biol Chem. 1967 Jun 10;242(11):2780–2789. [PubMed] [Google Scholar]
  10. Kawakami T. G., Huff S. D., Buckley P. M., Dungworth D. L., Synder S. P., Gilden R. V. C-type virus associated with gibbon lymphosarcoma. Nat New Biol. 1972 Feb 9;235(58):170–171. doi: 10.1038/newbio235170a0. [DOI] [PubMed] [Google Scholar]
  11. Lewis B. J., Abrell J. W., Smith R. G., Gallo R. C. Human DNA polymerase 3 (R-DNA polymerase): distinction from DNA polymerase I and reverse transcriptase. Science. 1974 Mar 1;183(4127):867–869. doi: 10.1126/science.183.4127.867. [DOI] [PubMed] [Google Scholar]
  12. Livingston D. M., Serxner L. E., Howk D. J., Hudson J., Todaro G. J. Characterization of a new murine cellular DNA polymerase. Proc Natl Acad Sci U S A. 1974 Jan;71(1):57–62. doi: 10.1073/pnas.71.1.57. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. McCaffrey R., Smoler D. F., Baltimore D. Terminal deoxynucleotidyl transferase in a case of childhood acute lymphoblastic leukemia. Proc Natl Acad Sci U S A. 1973 Feb;70(2):521–525. doi: 10.1073/pnas.70.2.521. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Riddick D. H., Gallo R. C. Correlation of transfer RNA methylase activity with growth and differentiation in normal and neoplastic tissues. Cancer Res. 1970 Oct;30(10):2484–2492. [PubMed] [Google Scholar]
  15. Ross J., Scolnick E. M., Todaro G. J., Aaronson S. A. Separation of murine cellular and murine leukaemia virus DNA polymerases. Nat New Biol. 1971 Jun 9;231(23):163–167. doi: 10.1038/newbio231163a0. [DOI] [PubMed] [Google Scholar]
  16. Sarngadharan M. G., Sarin P. S., Reitz M. S., Gallo R. C. Reverse transcriptase activity of human acute leukaemic cells: purification of the enzyme, response to AMV 70S RNA, and characterization of the DNA product. Nat New Biol. 1972 Nov 15;240(98):67–72. doi: 10.1038/newbio240067a0. [DOI] [PubMed] [Google Scholar]
  17. Scolnick E. M., Parks W. P., Todaro G. J., Aaronson S. A. Immunological characterization of primate C-type virus reverse transcriptases. Nat New Biol. 1972 Jan 12;235(54):35–40. doi: 10.1038/newbio235035a0. [DOI] [PubMed] [Google Scholar]
  18. Smith R. G., Gallo R. C. DNA-dependent DNA polymerases I and II from normal human-blood lymphocytes. Proc Natl Acad Sci U S A. 1972 Oct;69(10):2879–2884. doi: 10.1073/pnas.69.10.2879. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Theilen G. H., Gould D., Fowler M., Dungworth D. L. C-type virus in tumor tissue of a woolly monkey (Lagothrix spp.) with fibrosarcoma. J Natl Cancer Inst. 1971 Oct;47(4):881–889. [PubMed] [Google Scholar]
  20. Todaro G. J., Gallo R. C. Immunological relationship of DNA polymerase from human acute leukaemia cells and primate and mouse leukaemia virus reverse transcriptase. Nature. 1973 Jul 27;244(5413):206–209. doi: 10.1038/244206a0. [DOI] [PubMed] [Google Scholar]
  21. Todaro G. J., Huebner R. J. N.A.S. symposium: new evidence as the basis for increased efforts in cancer research. Proc Natl Acad Sci U S A. 1972 Apr;69(4):1009–1015. doi: 10.1073/pnas.69.4.1009. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Wolfe L. G., Deinhardt F., Theilen G. H., Rabin H., Kawakami T., Bustad L. K. Induction of tumors in marmoset monkeys by simian sarcoma virus, type 1 (Lagothrix): a preliminary report. J Natl Cancer Inst. 1971 Nov;47(5):1115–1120. [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES