Skip to main content
NCBI home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1990 Feb 1;171(2):489–501. doi: 10.1084/jem.171.2.489

The chromosome translocation (11;14)(p13;q11) associated with T cell acute leukemia. Asymmetric diversification of the translocational junctions

PMCID: PMC2187731  PMID: 2303782

Abstract

The t(11;14)(p13;q13) translocation associated with T cell acute lymphocytic leukemia generates two abnormal chromosomes, designated 11p+ and 14q-. To investigate the mechanism of t(11;14)(p13;q11) formation, we analyzed the translocation junctions of 11p+ and 14q- from two patients. The 11p+ junctions consisted of precise fusions of a pseudo recombination signal from chromosome 11 and the downstream recombination signal of the TCR D delta 2 gene segment from chromosome 14. In contrast, the 14q- junctions from both patients were diversified by random loss and addition of nucleotides at the translocation site. This asymmetric pattern of junctional diversification is typical of normal Ig/TCR gene rearrangement, and therefore implies that the t(11;14)(p13;q11) translocation arose due to aberrant activity of the Ig/TCR recombinase.

Full Text

The Full Text of this article is available as a PDF (925.5 KB).

Selected References

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

  1. Aguilera R. J., Akira S., Okazaki K., Sakano H. A pre-B cell nuclear protein that specifically interacts with the immunoglobulin V-J recombination sequences. Cell. 1987 Dec 24;51(6):909–917. doi: 10.1016/0092-8674(87)90578-2. [DOI] [PubMed] [Google Scholar]
  2. Alt F. W., Baltimore D. Joining of immunoglobulin heavy chain gene segments: implications from a chromosome with evidence of three D-JH fusions. Proc Natl Acad Sci U S A. 1982 Jul;79(13):4118–4122. doi: 10.1073/pnas.79.13.4118. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Alt F. W., Blackwell T. K., DePinho R. A., Reth M. G., Yancopoulos G. D. Regulation of genome rearrangement events during lymphocyte differentiation. Immunol Rev. 1986 Feb;89:5–30. doi: 10.1111/j.1600-065x.1986.tb01470.x. [DOI] [PubMed] [Google Scholar]
  4. Aurias A., Dutrillaux B. Probable involvement of immunoglobulin superfamily genes in most recurrent chromosomal rearrangements from ataxia telangiectasia. Hum Genet. 1986 Mar;72(3):210–214. doi: 10.1007/BF00291879. [DOI] [PubMed] [Google Scholar]
  5. Baer R., Boehm T., Yssel H., Spits H., Rabbitts T. H. Complex rearrangements within the human J delta-C delta/J alpha-C alpha locus and aberrant recombination between J alpha segments. EMBO J. 1988 Jun;7(6):1661–1668. doi: 10.1002/j.1460-2075.1988.tb02993.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bakhshi A., Wright J. J., Graninger W., Seto M., Owens J., Cossman J., Jensen J. P., Goldman P., Korsmeyer S. J. Mechanism of the t(14;18) chromosomal translocation: structural analysis of both derivative 14 and 18 reciprocal partners. Proc Natl Acad Sci U S A. 1987 Apr;84(8):2396–2400. doi: 10.1073/pnas.84.8.2396. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Benton W. D., Davis R. W. Screening lambdagt recombinant clones by hybridization to single plaques in situ. Science. 1977 Apr 8;196(4286):180–182. doi: 10.1126/science.322279. [DOI] [PubMed] [Google Scholar]
  8. Blackwell T. K., Malynn B. A., Pollock R. R., Ferrier P., Covey L. R., Fulop G. M., Phillips R. A., Yancopoulos G. D., Alt F. W. Isolation of scid pre-B cells that rearrange kappa light chain genes: formation of normal signal and abnormal coding joins. EMBO J. 1989 Mar;8(3):735–742. doi: 10.1002/j.1460-2075.1989.tb03433.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Boehm T., Baer R., Lavenir I., Forster A., Waters J. J., Nacheva E., Rabbitts T. H. The mechanism of chromosomal translocation t(11;14) involving the T-cell receptor C delta locus on human chromosome 14q11 and a transcribed region of chromosome 11p15. EMBO J. 1988 Feb;7(2):385–394. doi: 10.1002/j.1460-2075.1988.tb02825.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Boehm T., Buluwela L., Williams D., White L., Rabbitts T. H. A cluster of chromosome 11p13 translocations found via distinct D-D and D-D-J rearrangements of the human T cell receptor delta chain gene. EMBO J. 1988 Jul;7(7):2011–2017. doi: 10.1002/j.1460-2075.1988.tb03040.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Boehm T., Lavenir I., Forster A., Wadey R. B., Cowell J. K., Harbott J., Lampert F., Waters J., Sherrington P., Couillin P. The T-ALL specific t(11;14)(p13;q11) translocation breakpoint cluster region is located near to the Wilms' tumour predisposition locus. Oncogene. 1988 Dec;3(6):691–695. [PubMed] [Google Scholar]
  12. Boehm T., Mengle-Gaw L., Kees U. R., Spurr N., Lavenir I., Forster A., Rabbitts T. H. Alternating purine-pyrimidine tracts may promote chromosomal translocations seen in a variety of human lymphoid tumours. EMBO J. 1989 Sep;8(9):2621–2631. doi: 10.1002/j.1460-2075.1989.tb08402.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Champagne E., Takihara Y., Sagman U., de Sousa J., Burrow S., Lewis W. H., Mak T. W., Minden M. D. The T-cell receptor delta chain locus is disrupted in the T-ALL associated t(11;14)(p13;q11) translocation. Blood. 1989 May 1;73(6):1672–1676. [PubMed] [Google Scholar]
  14. Erikson J., Williams D. L., Finan J., Nowell P. C., Croce C. M. Locus of the alpha-chain of the T-cell receptor is split by chromosome translocation in T-cell leukemias. Science. 1985 Aug 23;229(4715):784–786. doi: 10.1126/science.3875152. [DOI] [PubMed] [Google Scholar]
  15. Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
  16. Hayashi Y., Ohta Y., Kaneko Y., Sakurai M., Bessho F., Saito F. 11;14 translocation in childhood T-cell acute lymphoblastic leukemia. Jpn J Cancer Res. 1985 Mar;76(3):160–161. [PubMed] [Google Scholar]
  17. Hesse J. E., Lieber M. R., Gellert M., Mizuuchi K. Extrachromosomal DNA substrates in pre-B cells undergo inversion or deletion at immunoglobulin V-(D)-J joining signals. Cell. 1987 Jun 19;49(6):775–783. doi: 10.1016/0092-8674(87)90615-5. [DOI] [PubMed] [Google Scholar]
  18. Hockett R. D., de Villartay J. P., Pollock K., Poplack D. G., Cohen D. I., Korsmeyer S. J. Human T-cell antigen receptor (TCR) delta-chain locus and elements responsible for its deletion are within the TCR alpha-chain locus. Proc Natl Acad Sci U S A. 1988 Dec;85(24):9694–9698. doi: 10.1073/pnas.85.24.9694. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Karn J., Matthes H. W., Gait M. J., Brenner S. A new selective phage cloning vector, lambda 2001, with sites for XbaI, BamHI, HindIII, EcoRI, SstI and XhoI. Gene. 1984 Dec;32(1-2):217–224. doi: 10.1016/0378-1119(84)90049-0. [DOI] [PubMed] [Google Scholar]
  20. Kronenberg M., Siu G., Hood L. E., Shastri N. The molecular genetics of the T-cell antigen receptor and T-cell antigen recognition. Annu Rev Immunol. 1986;4:529–591. doi: 10.1146/annurev.iy.04.040186.002525. [DOI] [PubMed] [Google Scholar]
  21. Lewis S., Gifford A., Baltimore D. DNA elements are asymmetrically joined during the site-specific recombination of kappa immunoglobulin genes. Science. 1985 May 10;228(4700):677–685. doi: 10.1126/science.3158075. [DOI] [PubMed] [Google Scholar]
  22. Lewis W. H., Michalopoulos E. E., Williams D. L., Minden M. D., Mak T. W. Breakpoints in the human T-cell antigen receptor alpha-chain locus in two T-cell leukaemia patients with chromosomal translocations. Nature. 1985 Oct 10;317(6037):544–546. doi: 10.1038/317544a0. [DOI] [PubMed] [Google Scholar]
  23. Lieber M. R., Hesse J. E., Lewis S., Bosma G. C., Rosenberg N., Mizuuchi K., Bosma M. J., Gellert M. The defect in murine severe combined immune deficiency: joining of signal sequences but not coding segments in V(D)J recombination. Cell. 1988 Oct 7;55(1):7–16. doi: 10.1016/0092-8674(88)90004-9. [DOI] [PubMed] [Google Scholar]
  24. Lieber M. R., Hesse J. E., Mizuuchi K., Gellert M. Lymphoid V(D)J recombination: nucleotide insertion at signal joints as well as coding joints. Proc Natl Acad Sci U S A. 1988 Nov;85(22):8588–8592. doi: 10.1073/pnas.85.22.8588. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. McCormack W. T., Tjoelker L. W., Carlson L. M., Petryniak B., Barth C. F., Humphries E. H., Thompson C. B. Chicken IgL gene rearrangement involves deletion of a circular episome and addition of single nonrandom nucleotides to both coding segments. Cell. 1989 Mar 10;56(5):785–791. doi: 10.1016/0092-8674(89)90683-1. [DOI] [PubMed] [Google Scholar]
  26. Messing J., Vieira J. A new pair of M13 vectors for selecting either DNA strand of double-digest restriction fragments. Gene. 1982 Oct;19(3):269–276. doi: 10.1016/0378-1119(82)90016-6. [DOI] [PubMed] [Google Scholar]
  27. Pridmore R. D. New and versatile cloning vectors with kanamycin-resistance marker. Gene. 1987;56(2-3):309–312. doi: 10.1016/0378-1119(87)90149-1. [DOI] [PubMed] [Google Scholar]
  28. Raimondi S. C., Behm F. G., Roberson P. K., Pui C. H., Rivera G. K., Murphy S. B., Williams D. L. Cytogenetics of childhood T-cell leukemia. Blood. 1988 Nov;72(5):1560–1566. [PubMed] [Google Scholar]
  29. Saiki R. K., Gelfand D. H., Stoffel S., Scharf S. J., Higuchi R., Horn G. T., Mullis K. B., Erlich H. A. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science. 1988 Jan 29;239(4839):487–491. doi: 10.1126/science.2448875. [DOI] [PubMed] [Google Scholar]
  30. Sanger F., Coulson A. R., Barrell B. G., Smith A. J., Roe B. A. Cloning in single-stranded bacteriophage as an aid to rapid DNA sequencing. J Mol Biol. 1980 Oct 25;143(2):161–178. doi: 10.1016/0022-2836(80)90196-5. [DOI] [PubMed] [Google Scholar]
  31. Satyanarayana K., Hata S., Devlin P., Roncarolo M. G., De Vries J. E., Spits H., Strominger J. L., Krangel M. S. Genomic organization of the human T-cell antigen-receptor alpha/delta locus. Proc Natl Acad Sci U S A. 1988 Nov;85(21):8166–8170. doi: 10.1073/pnas.85.21.8166. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Showe L. C., Croce C. M. The role of chromosomal translocations in B- and T-cell neoplasia. Annu Rev Immunol. 1987;5:253–277. doi: 10.1146/annurev.iy.05.040187.001345. [DOI] [PubMed] [Google Scholar]
  33. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  34. Takihara Y., Tkachuk D., Michalopoulos E., Champagne E., Reimann J., Minden M., Mak T. W. Sequence and organization of the diversity, joining, and constant region genes of the human T-cell delta-chain locus. Proc Natl Acad Sci U S A. 1988 Aug;85(16):6097–6101. doi: 10.1073/pnas.85.16.6097. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Tonegawa S. Somatic generation of antibody diversity. Nature. 1983 Apr 14;302(5909):575–581. doi: 10.1038/302575a0. [DOI] [PubMed] [Google Scholar]
  36. Tycko B., Reynolds T. C., Smith S. D., Sklar J. Consistent breakage between consensus recombinase heptamers of chromosome 9 DNA in a recurrent chromosomal translocation of human T cell leukemia. J Exp Med. 1989 Feb 1;169(2):369–377. doi: 10.1084/jem.169.2.369. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. White L., Meyer P. R., Benedict W. F. Establishment and characterization of a human T-cell leukemia line (LALW-2) in nude mice. J Natl Cancer Inst. 1984 May;72(5):1029–1038. [PubMed] [Google Scholar]
  38. Williams D. L., Look A. T., Melvin S. L., Roberson P. K., Dahl G., Flake T., Stass S. New chromosomal translocations correlate with specific immunophenotypes of childhood acute lymphoblastic leukemia. Cell. 1984 Jan;36(1):101–109. doi: 10.1016/0092-8674(84)90078-3. [DOI] [PubMed] [Google Scholar]
  39. Yoffe G., Schneider N., Van Dyk L., Yang C. Y., Siciliano M., Buchanan G., Capra J. D., Baer R. The chromosome translocation (11;14)(p13;q11) associated with T-cell acute lymphocytic leukemia: an 11p13 breakpoint cluster region. Blood. 1989 Jul;74(1):374–379. [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES