Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Timeline
  • Published:

Chromosome translocations: dangerous liaisons revisited

Nature Reviews Cancer volume 1, pages 245–250 (2001)Cite this article

Abstract

Although it has been clear for more than a century that the chromosomes in human tumour cells are often wildly abnormal, there has been controversy as to whether these changes are primary events or are merely secondary epiphenomena that reflect the genomic instability of these cells. The prevailing view for most of this period was that chromosome changes were secondary events. What happened to change this view?

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: The consequences of recurring chromosome translocations.
Figure 2: Chromosome rearrangements in acute myeloid leukaemia cells.

References

  1. Boveri, T. in Zur Frage der Entstehung maligner (Gustav Fischer, Jena, 1914).

    Google Scholar 

  2. Levan, A. Some current problems of cancer cytogenetics. Hereditas 57, 343–355 (1967).

    Article  CAS  PubMed  Google Scholar 

  3. Nowell, P. & Hungerford, D. A minute chromosome in human granulocytic leukemia. Science 132, 1497 (1960).

    Google Scholar 

  4. Rowley, J. D. A new consistent chromosomal abnormality in chronic myelogenous leukaemia identified by quinacrine fluorescence and Giemsa staining. Nature 243, 290–293 (1973).

    Article  CAS  PubMed  Google Scholar 

  5. de Klein, A. A. Cellular oncogene is translocated to the Philadelphia chromosome in chronic myelocytic leukemia. Nature 300, 765–767 (1982).

    Article  CAS  PubMed  Google Scholar 

  6. Heisterkamp, N. et al. Localization of the c-ABL oncogene adjacent to a translocation breakpoint in chronic myelocytic leukemia. Nature 306, 239–242 (1983).

    Article  CAS  PubMed  Google Scholar 

  7. Groffen, J. et al. Philadelphia chromosomal breakpoints are clustered within a limited region, BCR, on chromosome 22. Cell 36, 93–99 (1984).

    Article  CAS  PubMed  Google Scholar 

  8. Shtivelman, E., Lifschitz, B., Gale, R. P. & Canaani, E. Fused transcript of ABL and BCR genes in chronic myelogenous leukaemia. Nature 315, 550–554 (1985).

    Article  CAS  PubMed  Google Scholar 

  9. Jaffe, E. S., Harris, N. L., Stein, H. & Vardiman, J. W. (eds) World Health Organization Classification of Tumours, Pathology and Genetics: Tumours of the Hematopoietic and Lymphoid Tissues (IARC, Lyon, 2001).

    Google Scholar 

  10. Berger, R., Chen, S. J. & Chen, Z. Philadelphia-positive acute leukemia. Cytogenetic and molecular aspects. Cancer Genet. Cytogenet. 44, 143–152 (1990).

    Article  CAS  PubMed  Google Scholar 

  11. Hermans, A. et al. Unique fusion of BCR and c-ABL genes in Philadelphia chromosome positive acute lymphoblastic leukemia. Cell 64, 343 (1987).

    Google Scholar 

  12. Witte, O. N., Dasgupta, A. & Baltimore, D. Abelson murine leukemia virus protein is phosphorylated in vitro to form phosphotyrosine. Nature 281, 396–398 (1980).

    Article  Google Scholar 

  13. Konopka, J. B., Watanabe, S. M. & Witte, O. N. An alteration of the human c-ABL protein in K562 leukemia cells unmasks associated tyrosine kinase activity. Cell 37, 1035–1042 (1984).

    Article  CAS  PubMed  Google Scholar 

  14. Daley, G. Q., Van Etten, R. A. & Baltimore, D. Induction of chronic myelogenous leukemia in mice by the p210 BCR/ABL gene of the Philadelphia chromosome. Science 247, 824 (1990).

    Article  CAS  PubMed  Google Scholar 

  15. Fialkow, P. J. in Genes and Cancer (eds Bishop, J. M., Rowley, J. D. & Greaves, M.) 215–226 (Alan R. Liss, New York, 1984).

    Google Scholar 

  16. Druker, B. J. et al. Activity of a specific inhibitor of the BCR-ABL tyrosine kinase in the blast crisis of chronic myeloid leukemia and acute lymphoblastic leukemia with the Philadelphia chromosome. N. Engl. J. Med. 344, 1038–1042 (2001).

    Article  CAS  PubMed  Google Scholar 

  17. Zech, L., Haglund, U., Nilsson, K. & Klein, G. Characteristic chromosomal abnormalities in biopsies and lymphoid-cell lines from patients with Burkitt and non-Burkitt lymphomas. Int. J. Cancer 17, 47–56 (1976).

    Article  CAS  PubMed  Google Scholar 

  18. Dalla-Favera, R. et al. Human c-MYC onc gene is located on the region of chromosome 8 that is translocated in Burkitt lymphoma cells. Proc. Natl Acad. Sci. USA 79, 7824–7827 (1982).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Taub, R. et al. Translocation of the c-MYC gene into the immunoglobulin heavy chain locus in human Burkitt lymphoma and murine plasmacytoma cells. Proc. Natl Acad. Sci. USA 79, 7837–7841 (1982).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. ar-Rushdi, A. et al. Differential expression of the translocated and the untranslocated c-MYC oncogene in Burkitt lymphoma. Science 222, 390–393 (1983).

    Article  CAS  PubMed  Google Scholar 

  21. Adams, J. M. et al. The c– Myc oncogene driven by immunoglobulin enhancers induces lymphoid malignancy in transgenic mice. Nature 318, 6046 (1985).

  22. Fukuhara, S., Rowley, J. D., Variakojis, D. & Golomb, H. M. Chromosome abnormalities in poorly differentiated lymphocytic leukemia. Cancer Res. 39, 3119–3128 (1979).

    CAS  PubMed  Google Scholar 

  23. Tsujimoto, Y., Finger, L. R., Yunis, J., Nowell, P. C. & Croce, C. M. Cloning of the chromosome breakpoint of neoplastic B cells with the t(14;18) chromosome translocation. Science 266, 1097–1099 (1984).

    Article  Google Scholar 

  24. Vaux, D. L., Cory, S. & Adams, J. M. Bcl-2 gene promotes haemopoietic cell survival and cooperates with c-Myc to immortalize pre-B cells. Nature 335, 440–442 (1988).

    Article  CAS  PubMed  Google Scholar 

  25. Rowley, J. D. Identification of a translocation with quinacrine fluorescence in a patient with acute leukemia. Ann. Genet. 16, 109–112 (1973).

    CAS  PubMed  Google Scholar 

  26. Miyoshi, H. et al. The t(8;21) breakpoints on chromosome 21 in acute myeloid leukemia clustered within a limited region of a novel gene, AML1. Proc. Natl Acad. Sci. USA 88, 10431 (1991).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Wang, Q. et al. The CBFβ subunit is essential for CBFα2 (AML1) function in vivo. Cell 87, 697–708 (1996).

    Article  CAS  PubMed  Google Scholar 

  28. Le Beau, M. M. et al. Association of inv(16)(p13q22) with abnormal marrow eosinophils in acute myelomonocytic leukemia: a unique cytogenetic-clinicopathologic association. N. Engl. J. Med. 309, 630–636 (1983).

    Article  CAS  PubMed  Google Scholar 

  29. Liu, P. et al. Fusion between transcription factor CBF ?/PEBP2 ? and ? myosin heavy chain in acute myeloid leukemia. Science 261, 1041–1044 (1993).

    Article  CAS  PubMed  Google Scholar 

  30. Finger, L. R., Harvey, R. C., Moore, R. C., Showe, L. C. & Croce, C. M. A common mechanism of chromosomal translocation in T and B cell neoplasia. Science 234, 982–985 (1986).

    Article  CAS  PubMed  Google Scholar 

  31. Rabbitts, T. H., Boehm, T. & Mengle-Gaw, L. Chromosomal abnormalities in lymphoid tumors: mechanism and role in tumor pathogenesis. Trends Genet. 4, 300 (1988).

    Article  CAS  PubMed  Google Scholar 

  32. Hatano, M., Roberts, C. W., Minden, M., Crist, W. M. & Korsmeyer, S. J. Deregulation of a homeobox gene, HOX11, by the t(10;14) in the T cell leukemia. Science 253, 79 (1991).

    Article  CAS  PubMed  Google Scholar 

  33. Schichman, S., Canaani, E. & Croce, C. M. Self-fusion of the ALL-1 gene: a new genetic mechanism for acute leukemia. J. Am. Med. Assoc. 273, 571–576 (1995).

    Article  CAS  Google Scholar 

  34. Strissel, P. A. et al. DNA structural properties of AF9 are similar to MLL and could act as recombination hot spots resulting in MLL/AF9 translocations and leukemogenesis. Hum. Mol. Genet. 9, 1671–1679 (2000).

    Article  CAS  PubMed  Google Scholar 

  35. Stanulla, M., Wang, J., Chervinsky, D. S., Thandla, S. & Aplan, P. D. DNA cleavage within the MLL breakpoint cluster region is a specific event which occurs as part of higher-order chromatin fragmentation during the initial stages of apoptosis. Mol. Cell. Biol. 17, 4070–4079 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Mitelman, F. The Third International Workshop on Chromosomes in Leukemia. Lund, Sweden, July 21–25, 1980. Introduction. Cancer Genet. Cytogenet. 4, 96–98 (1981).

    Article  Google Scholar 

  37. Bloomfield, C. D., Goldman, A., Hossfeld D. & de la Chapelle, A. Fourth International Workshop on Chromosomes in Leukemia 1982: clinical significance of chromosomal abnormalities in acute nonlymphoblastic leukemia. Cancer Genet. Cytogenet. 11, 332–350 (1984).

    Article  CAS  PubMed  Google Scholar 

  38. Grimwade, D. et al. The importance of diagnostic cytogenetics on outcome in AML: analysis of 1,612 patients entered into the MRC AML 10 trial. The Medical Research Council Adult and Children's Leukaemia Working Parties. Blood 92, 2322–2333 (1998).

    CAS  PubMed  Google Scholar 

  39. Huang, M. E. et al. Use of all- trans retinoic acid in the treatment of acute promyelocytic leukemia. Blood 72, 567–572 (1988).

    CAS  PubMed  Google Scholar 

  40. Nucifora, G. & Rowley, J. D. AML1 and the 8;21 and 3;21 translocations in acute and chronic myeloid leukemia. Blood 86, 1–14 (1995).

    CAS  PubMed  Google Scholar 

  41. Uckun, F. M. et al. Clinical significance of MLL-AF4 fusion transcript expression in the absence of a cytogenetically detectable t(4;11)(q21;q23) chromosomal translocation. Blood 92, 810–821 (1998).

    CAS  PubMed  Google Scholar 

  42. Rowley, J. D., Golomb, H. M. & Vardiman, J. W. Nonrandom chromosomal abnormalities in acute nonlymphocytic leukemia in patients treated for Hodgkin's disease and non-Hodgkin lymphomas. Blood 50, 759–770 (1977).

    Google Scholar 

  43. Zhao, N. et al. Molecular delineation of the smallest commonly deleted region of chromosome 5 in malignant myeloid diseases to 1–1.5 Mb and preparation of a PAC-based physical map. Proc. Natl Acad. Sci. USA 94, 6948–6953 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Mitelman, F. Catalog of Chromosome Aberrations in Cancer 5th edn (Wiley–Liss, New York, 1994).

    Google Scholar 

  45. Olney, H.J., Gozzetti, A., & Rowley, J.D. in Hematology of Infancy and Childhood 6th edn (eds. Nathan, D., Orkin, S., Look, T. & Ginsburg, D. (WB Saunders, Philadelphia, 2002, in the press).

    Google Scholar 

  46. Chaganti, R., Nanjangud, G., Schmidt, H. & Teruya-Feldstein, J. Recurring chromosomal abnormalities in non-Hodgkin's lymphoma: biologic and clinical significance. Sem. Hematol. 37, 396–411 (2000).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The research from my laboratory described in this paper was supported by the National Cancer Institute and the G. Harold and Leila Y. Mathers Foundation. I thank H. Olney, Y. Kobzev and S. Maaskant for their valuable assistance.

Author information

Authors and Affiliations

  1. the Department of Medicine, Section of Hematology/Oncology, University of Chicago Medical Center, 5841 South Maryland Avenue, MC 2115, Chicago, 60637, Illinois, USA

    Janet D. Rowley

Authors
  1. Janet D. Rowley
    View author publications

    You can also search for this author in PubMed Google Scholar

Supplementary information

Related links

Related links

DATABASES

CancerNet:

acute lymphoblastic leukaemia

acute myelocytic leukaemia

chronic myelogenous leukaemia

 LocusLink:

Abl

ABL

AML1

BCL2

BCR

CBFA

CBFB

ETO

HOX11

IGH

MLL

MYC

TCRA

 Medscape DrugInfo:

Glivec

FURTHER INFORMATION

F. E. Mitelman Database of Chromosome Aberrations in Cancer

Glossary

DICENTRIC CHROMOSOME

A chromosome that has two centromeres, formed by breakage and reunion of two chromosomes.

DNASE I HYPERSENSITIVE SITE

DNA sites that are open and accessible to cleavage by DNA-specific enzymes.

MULTIPLEX RT–PCR

Primers for several mRNAs are used in a single RT–PCR reaction, allowing amplification of many (6 –12) separate RNA templates. This technique can be used to screen cells for several translocations at once.

REAL-TIME RT–PCR

RT–PCR using a fluorescent probe that contains a 5′-fluorescent label and 3′-quencher dye. As reverse transcription occurs, the 5′-reporter dye is released and the level of fluorescence emission can be measured as the reaction is proceeding. This technique can be used throughout a patient's treatment programme to monitor the proportion of leukaemic cells that still carry a translocation-induced fusion mRNA.

RT–PCR

(Reverse transcriptase polymerase chain reaction). This technique can be used to amplify cDNA from an mRNA template, using sequence-specific primers. Primers for fusion mRNAs created by known chromosome translocations can be used to identify cancer cells.

RING CHROMOSOME

Two breaks occur in the same chromosome, on opposite sides of the centromere. In these chromosomes, the ends of the centric fragment fuse.

SOMATIC CELL HYBRID

Fusion of cells from two species, often rodent and human. This causes loss of chromosomes, reducing the number of chromosomes from one species. These were important early tools used for mapping the location of genes to chromosomes.

TOPOISOMERASE II

An enzyme that binds to double-stranded DNA, cleaves both strands, passes one strand through the other to unwind the DNA and then relegates the broken ends.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rowley, J. Chromosome translocations: dangerous liaisons revisited. Nat Rev Cancer 1, 245–250 (2001). https://doi.org/10.1038/35106108

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/35106108

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing