Skip to main content
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
. 1983 Aug;80(16):5007–5011. doi: 10.1073/pnas.80.16.5007

Genetic analysis of the 15;17 chromosome translocation associated with acute promyelocytic leukemia.

D Sheer, L R Hiorns, K F Stanley, P N Goodfellow, D M Swallow, S Povey, N Heisterkamp, J Groffen, J R Stephenson, E Solomon
PMCID: PMC384177  PMID: 6576373

Abstract

Somatic cell hybrids have been constructed between a thymidine kinase-deficient mouse cell line and blood leukocytes from a patient with acute promyelocytic leukemia showing the 15q+;17q- chromosome translocation frequently associated with this disease. One hybrid contains the 15q+ translocation chromosome and very little other human material. We have shown that the c-fes oncogene, which has been mapped to chromosome 15, is not present in this hybrid and, therefore, probably is translocated to the 17q- chromosome. Analysis of the genetic markers present in this hybrid has enabled a more precise localization of the translocation breakpoints on chromosomes 15 and 17. Our experiments also have enabled an ordering and more precise mapping of several genetic markers on chromosomes 15 and 17.

Full text

PDF
5010

Images in this article

Selected References

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

  1. Bai Y., Sheer D., Hiorns L., Knowles R. W., Tunnacliffe A. A monoclonal antibody recognizing a cell surface antigen coded for by a gene on human chromosome 17. Ann Hum Genet. 1982 Oct;46(Pt 4):337–347. doi: 10.1111/j.1469-1809.1982.tb01584.x. [DOI] [PubMed] [Google Scholar]
  2. Barbacid M., Beemon K., Devare S. G. Origin and functional properties of the major gene product of the Snyder-Theilen strain of feline sarcoma virus. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5158–5162. doi: 10.1073/pnas.77.9.5158. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bennett J. M., Catovsky D., Daniel M. T., Flandrin G., Galton D. A., Gralnick H. R., Sultan C. Proposals for the classification of the acute leukaemias. French-American-British (FAB) co-operative group. Br J Haematol. 1976 Aug;33(4):451–458. doi: 10.1111/j.1365-2141.1976.tb03563.x. [DOI] [PubMed] [Google Scholar]
  4. Bernstein R., Mendelow B., Pinto M. R., Morcom G., Bezwoda W. Complex translocations involving chromosomes 15 and 17 in acute promyelocytic leukaemia. Br J Haematol. 1980 Oct;46(2):311–314. doi: 10.1111/j.1365-2141.1980.tb05972.x. [DOI] [PubMed] [Google Scholar]
  5. Blair D. G., Oskarsson M., Wood T. G., McClements W. L., Fischinger P. J., Vande Woude G. G. Activation of the transforming potential of a normal cell sequence: a molecular model for oncogenesis. Science. 1981 May 22;212(4497):941–943. doi: 10.1126/science.7233190. [DOI] [PubMed] [Google Scholar]
  6. Bobrow M., Cross J. Differential staining of human and mouse chromosomes in interspecific cell hybrids. Nature. 1974 Sep 6;251(5470):77–79. doi: 10.1038/251077a0. [DOI] [PubMed] [Google Scholar]
  7. Brodsky F. M., Bodmer W. F., Parham P. Characterization of a monoclonal anti-beta 2-microglobulin antibody and its use in the genetic and biochemical analysis of major histocompatibility antigens. Eur J Immunol. 1979 Jul;9(7):536–545. doi: 10.1002/eji.1830090709. [DOI] [PubMed] [Google Scholar]
  8. Calame K., Kim S., Lalley P., Hill R., Davis M., Hood L. Molecular cloning of translocations involving chromosome 15 and the immunoglobulin C alpha gene from chromosome 12 in two murine plasmacytomas. Proc Natl Acad Sci U S A. 1982 Nov;79(22):6994–6998. doi: 10.1073/pnas.79.22.6994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Caspersson T., Lomakka G., Zech L. The 24 fluorescence patterns of the human metaphase chromosomes - distinguishing characters and variability. Hereditas. 1972;67(1):89–102. doi: 10.1111/j.1601-5223.1971.tb02363.x. [DOI] [PubMed] [Google Scholar]
  10. Chang E. H., Furth M. E., Scolnick E. M., Lowy D. R. Tumorigenic transformation of mammalian cells induced by a normal human gene homologous to the oncogene of Harvey murine sarcoma virus. Nature. 1982 Jun 10;297(5866):479–483. doi: 10.1038/297479a0. [DOI] [PubMed] [Google Scholar]
  11. Chern C. J., Kennett R., Engel E., Mellman W. J., Croce C. M. Assignment of the structural genes for the alpha subunit of hexosaminidase A, mannosephosphate isomerase, and pyruvate kinase to the region q22-qter of human chromosome 15. Somatic Cell Genet. 1977 Nov;3(6):553–560. doi: 10.1007/BF01539065. [DOI] [PubMed] [Google Scholar]
  12. Church R. L., SundarRaj N., McDougall J. K. Regional chromosome mapping of the human skin type I procollagen gene using adenovirus 12-fragmentation of human-mouse somatic cell hybrids. Cytogenet Cell Genet. 1980;27(1):24–30. doi: 10.1159/000131460. [DOI] [PubMed] [Google Scholar]
  13. Crews S., Barth R., Hood L., Prehn J., Calame K. Mouse c-myc oncogene is located on chromosome 15 and translocated to chromosome 12 in plasmacytomas. Science. 1982 Dec 24;218(4579):1319–1321. doi: 10.1126/science.7146913. [DOI] [PubMed] [Google Scholar]
  14. Croce C. M., Knowles B. B., Koprowski H. Preferential retention of the human chromosome C-7 in human-(thymidine kinase deficient) mouse hybrid cells. Exp Cell Res. 1973 Dec;82(2):457–461. doi: 10.1016/0014-4827(73)90366-2. [DOI] [PubMed] [Google Scholar]
  15. Dalla-Favera R., Bregni M., Erikson J., Patterson D., Gallo R. C., Croce C. M. Human c-myc onc gene is located on the region of chromosome 8 that is translocated in Burkitt lymphoma cells. Proc Natl Acad Sci U S A. 1982 Dec;79(24):7824–7827. doi: 10.1073/pnas.79.24.7824. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Dalla-Favera R., Franchini G., Martinotti S., Wong-Staal F., Gallo R. C., Croce C. M. Chromosomal assignment of the human homologues of feline sarcoma virus and avian myeloblastosis virus onc genes. Proc Natl Acad Sci U S A. 1982 Aug;79(15):4714–4717. doi: 10.1073/pnas.79.15.4714. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Dalla-Favera R., Gallo R. C., Giallongo A., Croce C. M. Chromosomal localization of the human homolog (c-sis) of the simian sarcoma virus onc gene. Science. 1982 Nov 12;218(4573):686–688. doi: 10.1126/science.6291150. [DOI] [PubMed] [Google Scholar]
  18. Der C. J., Krontiris T. G., Cooper G. M. Transforming genes of human bladder and lung carcinoma cell lines are homologous to the ras genes of Harvey and Kirsten sarcoma viruses. Proc Natl Acad Sci U S A. 1982 Jun;79(11):3637–3640. doi: 10.1073/pnas.79.11.3637. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Elsevier S. M., Kucherlapati R. S., Nichols E. A., Creagan R. P., Giles R. E., Ruddle F. H., Willecke K., McDougall J. K. Assignment of the gene for galactokinase to human chromosome 17 and its regional localisation to band q21-22. Nature. 1974 Oct 18;251(5476):633–636. doi: 10.1038/251633a0. [DOI] [PubMed] [Google Scholar]
  20. Erikson J., Martinis J., Croce C. M. Assignment of the genes for human lambda immunoglobulin chains to chromosome 22. Nature. 1981 Nov 12;294(5837):173–175. doi: 10.1038/294173a0. [DOI] [PubMed] [Google Scholar]
  21. Feldman R. A., Hanafusa T., Hanafusa H. Characterization of protein kinase activity associated with the transforming gene product of Fujinami sarcoma virus. Cell. 1980 Dec;22(3):757–765. doi: 10.1016/0092-8674(80)90552-8. [DOI] [PubMed] [Google Scholar]
  22. Galfre G., Howe S. C., Milstein C., Butcher G. W., Howard J. C. Antibodies to major histocompatibility antigens produced by hybrid cell lines. Nature. 1977 Apr 7;266(5602):550–552. doi: 10.1038/266550a0. [DOI] [PubMed] [Google Scholar]
  23. Groffen J., Heisterkamp N., Grosveld F., Van de Ven W., Stephenson J. R. Isolation of human oncogene sequences (v-fes homolog) from a cosmid library. Science. 1982 Jun 4;216(4550):1136–1138. doi: 10.1126/science.6281890. [DOI] [PubMed] [Google Scholar]
  24. Groffen J., Heisterkamp N., Shibuya M., Hanafusa H., Stephenson J. R. Transforming genes of avian (v-fps) and mammalian (v-fes) retroviruses correspond to a common cellular locus. Virology. 1983 Mar;125(2):480–486. doi: 10.1016/0042-6822(83)90219-2. [DOI] [PubMed] [Google Scholar]
  25. Heisterkamp N., Groffen J., Stephenson J. R., Spurr N. K., Goodfellow P. N., Solomon E., Carritt B., Bodmer W. F. Chromosomal localization of human cellular homologues of two viral oncogenes. Nature. 1982 Oct 21;299(5885):747–749. doi: 10.1038/299747a0. [DOI] [PubMed] [Google Scholar]
  26. Huerre C., Junien C., Weil D., Chu M. L., Morabito M., Van Cong N., Myers J. C., Foubert C., Gross M. S., Prockop D. J. Human type I procollagen genes are located on different chromosomes. Proc Natl Acad Sci U S A. 1982 Nov;79(21):6627–6630. doi: 10.1073/pnas.79.21.6627. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. KIT S., DUBBS D. R., PIEKARSKI L. J., HSU T. C. DELETION OF THYMIDINE KINASE ACTIVITY FROM L CELLS RESISTANT TO BROMODEOXYURIDINE. Exp Cell Res. 1963 Aug;31:297–312. doi: 10.1016/0014-4827(63)90007-7. [DOI] [PubMed] [Google Scholar]
  28. Kirsch I. R., Morton C. C., Nakahara K., Leder P. Human immunoglobulin heavy chain genes map to a region of translocations in malignant B lymphocytes. Science. 1982 Apr 16;216(4543):301–303. doi: 10.1126/science.6801764. [DOI] [PubMed] [Google Scholar]
  29. Kondo K., Sasaki M. Further cytogenetic studies on acute promyelocytic leukemia. Cancer Genet Cytogenet. 1982 May;6(1):39–46. doi: 10.1016/0165-4608(82)90019-x. [DOI] [PubMed] [Google Scholar]
  30. Köhler G., Milstein C. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature. 1975 Aug 7;256(5517):495–497. doi: 10.1038/256495a0. [DOI] [PubMed] [Google Scholar]
  31. LITTLEFIELD J. W. SELECTION OF HYBRIDS FROM MATINGS OF FIBROBLASTS IN VITRO AND THEIR PRESUMED RECOMBINANTS. Science. 1964 Aug 14;145(3633):709–710. doi: 10.1126/science.145.3633.709. [DOI] [PubMed] [Google Scholar]
  32. McBride O. W., Swan D. C., Santos E., Barbacid M., Tronick S. R., Aaronson S. A. Localization of the normal allele of T24 human bladder carcinoma oncogene to chromosome 11. Nature. 1982 Dec 23;300(5894):773–774. doi: 10.1038/300773a0. [DOI] [PubMed] [Google Scholar]
  33. Nabholz M., Miggiano V., Bodmer W. Genetic analysis with human--mouse somatic cell hybrids. Nature. 1969 Jul 26;223(5204):358–363. doi: 10.1038/223358a0. [DOI] [PubMed] [Google Scholar]
  34. Neel B. G., Jhanwar S. C., Chaganti R. S., Hayward W. S. Two human c-onc genes are located on the long arm of chromosome 8. Proc Natl Acad Sci U S A. 1982 Dec;79(24):7842–7846. doi: 10.1073/pnas.79.24.7842. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Pajunen L., Solomon E., Burgess S., Bobrow M., Povey S., Swallow D. Regional mapping of chromosome 15. Cytogenet Cell Genet. 1978;22(1-6):511–512. doi: 10.1159/000131010. [DOI] [PubMed] [Google Scholar]
  36. Parada L. F., Tabin C. J., Shih C., Weinberg R. A. Human EJ bladder carcinoma oncogene is homologue of Harvey sarcoma virus ras gene. Nature. 1982 Jun 10;297(5866):474–478. doi: 10.1038/297474a0. [DOI] [PubMed] [Google Scholar]
  37. Pawson T., Guyden J., Kung T. H., Radke K., Gilmore T., Martin G. S. A strain of Fujinami sarcoma virus which is temperature-sensitive in protein phosphorylation and cellular transformation. Cell. 1980 Dec;22(3):767–775. doi: 10.1016/0092-8674(80)90553-x. [DOI] [PubMed] [Google Scholar]
  38. Ploegh H. L., Orr H. T., Strominger J. L. Major histocompatibility antigens: the human (HLA-A, -B, -C) and murine (H-2K, H-2D) class I molecules. Cell. 1981 May;24(2):287–299. doi: 10.1016/0092-8674(81)90318-4. [DOI] [PubMed] [Google Scholar]
  39. Prakash K., McBride O. W., Swan D. C., Devare S. G., Tronick S. R., Aaronson S. A. Molecular cloning and chromosomal mapping of a human locus related to the transforming gene of Moloney murine sarcoma virus. Proc Natl Acad Sci U S A. 1982 Sep;79(17):5210–5214. doi: 10.1073/pnas.79.17.5210. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Rechavi G., Givol D., Canaani E. Activation of a cellular oncogene by DNA rearrangement: possible involvement of an IS-like element. Nature. 1982 Dec 16;300(5893):607–611. doi: 10.1038/300607a0. [DOI] [PubMed] [Google Scholar]
  41. Reynolds F. H., Jr, Van de Ven W. J., Stephenson J. R. Feline sarcoma virus P115-associated protein kinase phosphorylates tyrosine. Identification of a cellular substrate conserved during evolution. J Biol Chem. 1980 Nov 25;255(22):11040–11047. [PubMed] [Google Scholar]
  42. Rowley J. D., Golomb H. M., Vardiman J., Fukuhara S., Dougherty C., Potter D. Further evidence for a non-random chromosomal abnormality in acute promyelocytic leukemia. Int J Cancer. 1977 Dec 15;20(6):869–872. doi: 10.1002/ijc.2910200608. [DOI] [PubMed] [Google Scholar]
  43. Rowley J. D. Identification of the constant chromosome regions involved in human hematologic malignant disease. Science. 1982 May 14;216(4547):749–751. doi: 10.1126/science.7079737. [DOI] [PubMed] [Google Scholar]
  44. Santos E., Tronick S. R., Aaronson S. A., Pulciani S., Barbacid M. T24 human bladder carcinoma oncogene is an activated form of the normal human homologue of BALB- and Harvey-MSV transforming genes. Nature. 1982 Jul 22;298(5872):343–347. doi: 10.1038/298343a0. [DOI] [PubMed] [Google Scholar]
  45. Seabright M. The use of proteolytic enzymes for the mapping of structural rearrangements in the chromosomes of man. Chromosoma. 1972;36(2):204–210. doi: 10.1007/BF00285214. [DOI] [PubMed] [Google Scholar]
  46. Shen-Ong G. L., Keath E. J., Piccoli S. P., Cole M. D. Novel myc oncogene RNA from abortive immunoglobulin-gene recombination in mouse plasmacytomas. Cell. 1982 Dec;31(2 Pt 1):443–452. doi: 10.1016/0092-8674(82)90137-4. [DOI] [PubMed] [Google Scholar]
  47. Shibuya M., Hanafusa T., Hanafusa H., Stephenson J. R. Homology exists among the transforming sequences of avian and feline sarcoma viruses. Proc Natl Acad Sci U S A. 1980 Nov;77(11):6536–6540. doi: 10.1073/pnas.77.11.6536. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Solomon E., Swallow D., Burgess S., Evans L. Assignment of the human acid alpha-glucosidase gene (alphaGLU) to chromosome 17 using somatic cell hybrids. Ann Hum Genet. 1979 Jan;42(3):273–281. doi: 10.1111/j.1469-1809.1979.tb00661.x. [DOI] [PubMed] [Google Scholar]
  49. Suggs S. V., Wallace R. B., Hirose T., Kawashima E. H., Itakura K. Use of synthetic oligonucleotides as hybridization probes: isolation of cloned cDNA sequences for human beta 2-microglobulin. Proc Natl Acad Sci U S A. 1981 Nov;78(11):6613–6617. doi: 10.1073/pnas.78.11.6613. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Swallow D. M., Solomon E., Pajunen L. Immunochemical analysis of the N-acetyl hexosaminidases in human-mouse hybrids made using a double selective system. Cytogenet Cell Genet. 1977;18(3):136–148. doi: 10.1159/000130758. [DOI] [PubMed] [Google Scholar]
  51. Swan D. C., McBride O. W., Robbins K. C., Keithley D. A., Reddy E. P., Aaronson S. A. Chromosomal mapping of the simian sarcoma virus onc gene analogue in human cells. Proc Natl Acad Sci U S A. 1982 Aug;79(15):4691–4695. doi: 10.1073/pnas.79.15.4691. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. TODARO G. J., GREEN H. Quantitative studies of the growth of mouse embryo cells in culture and their development into established lines. J Cell Biol. 1963 May;17:299–313. doi: 10.1083/jcb.17.2.299. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Taub R., Kirsch I., Morton C., Lenoir G., Swan D., Tronick S., Aaronson S., Leder P. Translocation of the c-myc gene into the immunoglobulin heavy chain locus in human Burkitt lymphoma and murine plasmacytoma cells. Proc Natl Acad Sci U S A. 1982 Dec;79(24):7837–7841. doi: 10.1073/pnas.79.24.7837. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Van Den Berghe H., Louwagie A., Broeckaert-Van Orshoven A., David G., Verwilghen R., Michaux J. L., Sokal G. Chromosome abnormalities in acute promyelocytic leukemia (APL). Cancer. 1979 Feb;43(2):558–562. doi: 10.1002/1097-0142(197902)43:2<558::aid-cncr2820430223>3.0.co;2-6. [DOI] [PubMed] [Google Scholar]
  55. Van de Ven W. J., Reynolds F. H., Jr, Stephenson J. R. The nonstructural components of polyproteins encoded by replication-defective mammalian transforming retroviruses are phosphorylated and have associated protein kinase activity. Virology. 1980 Feb;101(1):185–197. doi: 10.1016/0042-6822(80)90495-x. [DOI] [PubMed] [Google Scholar]
  56. Varmus H. E. Form and function of retroviral proviruses. Science. 1982 May 21;216(4548):812–820. doi: 10.1126/science.6177038. [DOI] [PubMed] [Google Scholar]
  57. Wallace D. C., Bunn C. L., Eisenstadt J. M. Cytoplasmic transfer of chloramphenicol resistance in human tissue culture cells. J Cell Biol. 1975 Oct;67(1):174–188. doi: 10.1083/jcb.67.1.174. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Weiss M. C., Green H. Human-mouse hybrid cell lines containing partial complements of human chromosomes and functioning human genes. Proc Natl Acad Sci U S A. 1967 Sep;58(3):1104–1111. doi: 10.1073/pnas.58.3.1104. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. de Klein A., van Kessel A. G., Grosveld G., Bartram C. R., Hagemeijer A., Bootsma D., Spurr N. K., Heisterkamp N., Groffen J., Stephenson J. R. A cellular oncogene is translocated to the Philadelphia chromosome in chronic myelocytic leukaemia. Nature. 1982 Dec 23;300(5894):765–767. doi: 10.1038/300765a0. [DOI] [PubMed] [Google Scholar]
  60. van Heyningen V., Bobrow M., Bodmer W. F., Gardiner S. E., Povey S., Hopkinson D. A. Chromosome assignment of some human enzyme loci: mitochondrial malate dehydrogenase to 7, mannosephosphate isomerase and pyruvate kinase to 15 and probably, esterase D to 13. Ann Hum Genet. 1975 Jan;38(3):295–303. doi: 10.1111/j.1469-1809.1975.tb00613.x. [DOI] [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