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. 1981 Aug;1(8):721–730. doi: 10.1128/mcb.1.8.721

Clonal analysis of the late stages of erythroleukemia induced by two distinct strains of Friend leukemia virus.

D Mager 1, M E MacDonald 1, I B Robson 1, T W Mak 1, A Bernstein 1
PMCID: PMC369352  PMID: 9279385

Abstract

We observed striking differences between the tumorigenic colony-forming cells present in the spleens of mice late after infection with the anemia-inducing strain of Friend leukemia virus (strain FV-A) and those present after infection with the polycythemia-inducing strain (strain FV-P). Cells within primary colonies derived from FV-A- and FV-P-transformed cells (CFU-FV-A and CFU-FV-P, respectively) contained hemoglobin and spectrin, indicating that the CFU-FV-A and CFU-FV-P were transformed erythroid progenitor cells. The proportion of cells containing hemoglobin was relatively high (> 25%) in newly isolated cell lines derived from CFU-FV-P colonies, whereas cell lines derived from CFU-FV-A colonies had only low levels (0 to 2%) of hemoglobin-containing cells. A high proportion of the cell lines derived from CFU-FV-A colonies responded to pure erythropoietin and accumulated spectrin and hemoglobin, whereas the cell lines derived from CFU-FV-P colonies did not. A cytogenetic analysis indicated that primary CFU-FV-P colony cells were diploid, whereas chromosomal aberrations were observed in the immediate progeny of CFU-FV-A. The presence of unique chromosomal markers in the majority of the cells within individual colonies derived from CFU-FV-A suggested that these colonies originated from single cells. Finally, leukemic progenitor cells transformed by strain FV-A appeared to have an extensive capacity to self-renew (i.e., form secondary colonies in methylcellulose), whereas a significant proportion of the corresponding cells transformed by strain FV-P did not. In addition, the self-renewal capacity of both CFU-FV-A and CFU-FV-P increased as the disease progressed. From these observations, we propose a model for the multistage nature of Friend disease; this model involves clonal evolution and expansion from a differentiating population with limited proliferative capacity to a population with a high capacity for self-renewal and proliferation.

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Selected References

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

  1. AXELRAD A. A., STEEVES R. A. ASSAY FOR FRIEND LEUKEMIA VIRUS: RAPID QUANTITATIVE METHOD BASED ON ENUMERATION OF MACROSCOPIC SPLEEN FOCI IN MICE. Virology. 1964 Nov;24:513–518. doi: 10.1016/0042-6822(64)90199-0. [DOI] [PubMed] [Google Scholar]
  2. BUFFETT R. F., FURTH J. A transplantable reticulum-cell sarcoma variant of Friend's viral leukemia. Cancer Res. 1959 Nov;19:1063–1069. [PubMed] [Google Scholar]
  3. Bernstein A., Mak T. W., Stephenson J. R. The Friend virus genome: evidence for the stable association of MuLV sequences and sequences involved in erythroleukemic transformation. Cell. 1977 Sep;12(1):287–294. doi: 10.1016/0092-8674(77)90206-9. [DOI] [PubMed] [Google Scholar]
  4. DAWSON P. J., FIELDSTEEL A. H., BOSTICK W. L. Pathologic studies of Friend virus leukemia and the development of a transplantable tumor in BALB/c mice. Cancer Res. 1963 Mar;23:349–354. [PubMed] [Google Scholar]
  5. Dexter T. M., Allen T. D., Scott D., Teich N. M. Isolation and characterisation of a bipotential haematopoietic cell line. Nature. 1979 Feb 8;277(5696):471–474. doi: 10.1038/277471a0. [DOI] [PubMed] [Google Scholar]
  6. Eisen H., Bach R., Emery R. Induction of spectrin in erythroleukemic cells transformed by Friend virus. Proc Natl Acad Sci U S A. 1977 Sep;74(9):3898–3902. doi: 10.1073/pnas.74.9.3898. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. FRIEND C. Cell-free transmission in adult Swiss mice of a disease having the character of a leukemia. J Exp Med. 1957 Apr 1;105(4):307–318. doi: 10.1084/jem.105.4.307. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. FRIEND C., HADDAD J. R. Tumor formation with transplants of spleen or liver from mice with virus-induced leukemia. J Natl Cancer Inst. 1960 Dec;25:1279–1285. [PubMed] [Google Scholar]
  9. Fioritoni G., Bertolini L., Torlontano G., Revoltella R. Cytochemical characteristics of leukopoietic differentiation in murine erythroleukemic (Friend) cells. Cancer Res. 1980 Mar;40(3):866–872. [PubMed] [Google Scholar]
  10. Friend C., Patuleia M. C., De Harven E. Erythrocytic maturation in vitro of murine (Friend) virus-induced leukemic cells. Natl Cancer Inst Monogr. 1966 Sep;22:505–522. [PubMed] [Google Scholar]
  11. Friend C., Scher W., Holland J. G., Sato T. Hemoglobin synthesis in murine virus-induced leukemic cells in vitro: stimulation of erythroid differentiation by dimethyl sulfoxide. Proc Natl Acad Sci U S A. 1971 Feb;68(2):378–382. doi: 10.1073/pnas.68.2.378. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Friend C. The phenomenon of differentiation in murine erythroleukemic cells. Harvey Lect. 1978;72:253–281. [PubMed] [Google Scholar]
  13. Golde D. W., Bersch N., Friend C., Tsuei D., Marovitz W. Transformation of DBA/2 mouse fetal liver cells infected in vitro by the anemic strain of Friend leukemia virus. Proc Natl Acad Sci U S A. 1979 Feb;76(2):962–966. doi: 10.1073/pnas.76.2.962. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Goldstein K., Preisler H. D., Lutton J. D., Zanjani E. D. Erythroid colony formation in vitro by dimethylsulfoxide-treated erythroleukemic cells. Blood. 1974 Dec;44(6):831–836. [PubMed] [Google Scholar]
  15. Hankins W. D., Troxler D. Polycythemia- and anemia-inducing erythroleukemia viruses exhibit differential erythroid transforming effects in vitro. Cell. 1980 Dec;22(3):693–699. doi: 10.1016/0092-8674(80)90545-0. [DOI] [PubMed] [Google Scholar]
  16. Harnden D. G., Taylor A. M. Chromosomes and neoplasia. Adv Hum Genet. 1979;9:1-70, 355-60. doi: 10.1007/978-1-4615-8276-2_1. [DOI] [PubMed] [Google Scholar]
  17. Hasthorpe S., Bol S. Erythropoietin responses and physical characterization of erythroid progenitor cells in Rauscher virus infected BALB/c mice. J Cell Physiol. 1979 Jul;100(1):77–86. doi: 10.1002/jcp.1041000108. [DOI] [PubMed] [Google Scholar]
  18. Horoszewicz J. S., Leong S. S., Carter W. A. Friend leukemia: rapid development of erythropoietin-independent hematopoietic precursors. J Natl Cancer Inst. 1975 Jan;54(1):265–267. doi: 10.1093/jnci/54.1.265. [DOI] [PubMed] [Google Scholar]
  19. Klein G. Lymphoma development in mice and humans: diversity of initiation is followed by convergent cytogenetic evolution. Proc Natl Acad Sci U S A. 1979 May;76(5):2442–2446. doi: 10.1073/pnas.76.5.2442. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Kluge N., Gaedicke G., Steinheider G., Dube S., Ostertag W. Globin synthesis in Friend-erythroleukemia mouse cells in protein- and lipid-free medium. Effects of dimethyl-sulfoxide, iron and erythropoietin. Exp Cell Res. 1974 Oct;88(2):257–262. doi: 10.1016/0014-4827(74)90239-0. [DOI] [PubMed] [Google Scholar]
  21. Liao S. K., Axelrad A. A. Erythropoietin-independent erythroid colony formation in vitro by hemopoietic cells of mice infected with friend virus. Int J Cancer. 1975 Mar 15;15(3):467–482. doi: 10.1002/ijc.2910150313. [DOI] [PubMed] [Google Scholar]
  22. MIRAND E. A., PRENTICE T., HOFFMAN J. G., GRACE J. T., Jr Effect of Friend virus in Swiss and DBA/1 mice on Fe59 uptake. Proc Soc Exp Biol Med. 1961 Feb;106:423–426. doi: 10.3181/00379727-106-26358. [DOI] [PubMed] [Google Scholar]
  23. MacDonald M. E., Johnson G. R., Bernstein A. Different pseudotypes of Friend spleen focus-forming virus induce polycythemia and erythropoietin-independent colony formation in serum-free medium. Virology. 1981 Apr 15;110(1):231–236. doi: 10.1016/0042-6822(81)90028-3. [DOI] [PubMed] [Google Scholar]
  24. MacDonald M. E., Mak T. W., Bernstein A. Erythroleukemia induction by replication-competent type C viruses cloned from the anemia- and polycythemia-inducing isolates of Friend leukemia virus. J Exp Med. 1980 Jun 1;151(6):1493–1503. doi: 10.1084/jem.151.6.1493. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. MacDonald M. E., Reynolds F. H., Jr, Van de Ven W. J., Stephenson J. R., Mak T. W., Bernstein A. Anemia- and polycythemia-inducing isolates of Friend spleen focus-forming virus. Biological and molecular evidence for two distinct viral genomes. J Exp Med. 1980 Jun 1;151(6):1477–1492. doi: 10.1084/jem.151.6.1477. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Mager D. L., Mak T. W., Bernstein A. Quantitative colony method for tumorigenic cells transformed by two distinct strains of Friend leukemia virus. Proc Natl Acad Sci U S A. 1981 Mar;78(3):1703–1707. doi: 10.1073/pnas.78.3.1703. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Mager D., Mak T. W., Bernstein A. Friend leukaemia virus-transformed cells, unlike normal stem cells, form spleen colonies in Sl/sld mice. Nature. 1980 Dec 11;288(5791):592–594. doi: 10.1038/288592a0. [DOI] [PubMed] [Google Scholar]
  28. Marchesi V. T., Steers E., Jr Selective solubilization of a protein component of the red cell membrane. Science. 1968 Jan 12;159(3811):203–204. doi: 10.1126/science.159.3811.203. [DOI] [PubMed] [Google Scholar]
  29. Marks P. A., Rifkind R. A. Erythroleukemic differentiation. Annu Rev Biochem. 1978;47:419–448. doi: 10.1146/annurev.bi.47.070178.002223. [DOI] [PubMed] [Google Scholar]
  30. McCulloch E. A., Siminovitch L., Till J. E., Russell E. S., Bernstein S. E. The cellular basis of the genetically determined hemopoietic defect in anemic mice of genotype Sl-Sld. Blood. 1965 Oct;26(4):399–410. [PubMed] [Google Scholar]
  31. Mirand E. A., Steeves R. A., Lange R. D., Grace J. T., Jr Virus-induced polycythemia in mice: erythropoiesis without erythropoietin. Proc Soc Exp Biol Med. 1968 Jul;128(3):844–849. doi: 10.3181/00379727-128-33139. [DOI] [PubMed] [Google Scholar]
  32. Miyake T., Kung C. K., Goldwasser E. Purification of human erythropoietin. J Biol Chem. 1977 Aug 10;252(15):5558–5564. [PubMed] [Google Scholar]
  33. Nowell P. C. The clonal evolution of tumor cell populations. Science. 1976 Oct 1;194(4260):23–28. doi: 10.1126/science.959840. [DOI] [PubMed] [Google Scholar]
  34. Orkin S. H., Harosi F. I., Leder P. Differentiation in erythroleukemic cells and their somatic hybrids. Proc Natl Acad Sci U S A. 1975 Jan;72(1):98–102. doi: 10.1073/pnas.72.1.98. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Ostertag W., Melderis H., Steinheider G., Kluge N., Dube S. Synthesis of mouse haemoglobin and globin mRNA in leukaemic cell cultures. Nat New Biol. 1972 Oct 25;239(95):231–234. doi: 10.1038/newbio239231a0. [DOI] [PubMed] [Google Scholar]
  36. Painter R. G., Sheetz M., Singer S. J. Detection and ultrastructural localization of human smooth muscle myosin-like molecules in human non-muscle cells by specific antibodies. Proc Natl Acad Sci U S A. 1975 Apr;72(4):1359–1363. doi: 10.1073/pnas.72.4.1359. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Preisler H. D., Shiraishi Y., Mori M., Sandberg A. A. Clones of Friend leukemia cells: differences in karyotypes and responsiveness to inducers of differentiation. Cell Differ. 1976 Oct;5(3):207–216. doi: 10.1016/0045-6039(76)90022-1. [DOI] [PubMed] [Google Scholar]
  38. Revoltella R., Bertolini L., Friend C. In vitro transformation of mouse bone marrow cells by the polycythemic strain of Friend leukemia virus. Proc Natl Acad Sci U S A. 1979 Mar;76(3):1464–1468. doi: 10.1073/pnas.76.3.1464. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Stephenson J. R., Axelrad A. A., McLeod D. L., Shreeve M. M. Induction of colonies of hemoglobin-synthesizing cells by erythropoietin in vitro. Proc Natl Acad Sci U S A. 1971 Jul;68(7):1542–1546. doi: 10.1073/pnas.68.7.1542. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. TSUCHIDA R., RICH M. A. CHROMOSOMAL ABERRATIONS IN VIRAL LEUKEMOGENESIS. I. FRIEND AND RAUSCHER LEUKEMIA. J Natl Cancer Inst. 1964 Jul;33:33–47. [PubMed] [Google Scholar]
  41. Tambourin P. E., Wendling F., Jasmin C., Smadja-Joffe F. The physiopathology of Friend leukemia. Leuk Res. 1979;3(3):117–129. doi: 10.1016/0145-2126(79)90009-2. [DOI] [PubMed] [Google Scholar]
  42. Till J. E., McCulloch E. A. Hemopoietic stem cell differentiation. Biochim Biophys Acta. 1980 Nov 26;605(4):431–459. doi: 10.1016/0304-419x(80)90009-8. [DOI] [PubMed] [Google Scholar]
  43. de Both N. J., Vermey M., van't Hull E., Klootwijk-van-Dijke E., van Griensven L. J., Mol J. N., Stoof T. J. A new erythroid cell line induced by Rauscher murine leukaemia virus. Nature. 1978 Apr 13;272(5654):626–628. doi: 10.1038/272626a0. [DOI] [PubMed] [Google Scholar]

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