Skip to main content
PMC home page
Nucleic Acids Research logoLink to Nucleic Acids Research
. 1989 Jan 11;17(1):1–10. doi: 10.1093/nar/17.1.1

Nucleotide sequence of both reciprocal translocation junction regions in a patient with Ph positive acute lymphoblastic leukaemia, with a breakpoint within the first intron of the BCR gene.

M J van der Feltz 1, M K Shivji 1, P B Allen 1, N Heisterkamp 1, J Groffen 1, L M Wiedemann 1
PMCID: PMC331530  PMID: 2911461

Abstract

Breakpoints on chromosome 22 in the translocation t(9;22) found in Philadelphia positive acute lymphoblastic leukaemia patients fall within two categories. In the first the breakpoint is localized within the breakpoint cluster region of the BCR gene, analogous to the chromosome 22 breakpoint in chronic myeloid leukaemia. The second category has a breakpoint 5' of this area, but still within the BCR gene. We have previously shown that these breakpoints occur within the first intron of the BCR gene and cloned the 9q+ junction from such a patient. We have now determined the sequences around the breakpoints on both translocation partners from this patient as well as the germline regions. The chromosome 9 ABL sequence around the breakpoint shows homology to the consensus Alu sequence whereas the chromosome 22 BCR sequence does not. At the junction there is a 6 bp duplication of the chromosome 22 sequence which is present both in the 9q+ and in the 22q- translocation products. Possible mechanisms for the generation of the translocation are discussed.

Full text

PDF
1

Images in this article

6Image
on p.6

Selected References

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

  1. Ben-Neriah Y., Daley G. Q., Mes-Masson A. M., Witte O. N., Baltimore D. The chronic myelogenous leukemia-specific P210 protein is the product of the bcr/abl hybrid gene. Science. 1986 Jul 11;233(4760):212–214. doi: 10.1126/science.3460176. [DOI] [PubMed] [Google Scholar]
  2. Chan L. C., Karhi K. K., Rayter S. I., Heisterkamp N., Eridani S., Powles R., Lawler S. D., Groffen J., Foulkes J. G., Greaves M. F. A novel abl protein expressed in Philadelphia chromosome positive acute lymphoblastic leukaemia. Nature. 1987 Feb 12;325(6105):635–637. doi: 10.1038/325635a0. [DOI] [PubMed] [Google Scholar]
  3. Clark S. S., McLaughlin J., Crist W. M., Champlin R., Witte O. N. Unique forms of the abl tyrosine kinase distinguish Ph1-positive CML from Ph1-positive ALL. Science. 1987 Jan 2;235(4784):85–88. doi: 10.1126/science.3541203. [DOI] [PubMed] [Google Scholar]
  4. Clark S. S., McLaughlin J., Timmons M., Pendergast A. M., Ben-Neriah Y., Dow L. W., Crist W., Rovera G., Smith S. D., Witte O. N. Expression of a distinctive BCR-ABL oncogene in Ph1-positive acute lymphocytic leukemia (ALL). Science. 1988 Feb 12;239(4841 Pt 1):775–777. doi: 10.1126/science.3422516. [DOI] [PubMed] [Google Scholar]
  5. Croce C. M. Role of chromosome translocations in human neoplasia. Cell. 1987 Apr 24;49(2):155–156. doi: 10.1016/0092-8674(87)90552-6. [DOI] [PubMed] [Google Scholar]
  6. De Klein A., Hagemeijer A., Bartram C. R., Houwen R., Hoefsloot L., Carbonell F., Chan L., Barnett M., Greaves M., Kleihauer E. bcr rearrangement and translocation of the c-abl oncogene in Philadelphia positive acute lymphoblastic leukemia. Blood. 1986 Dec;68(6):1369–1375. [PubMed] [Google Scholar]
  7. Dean M., Park M., Vande Woude G. F. Characterization of the rearranged tpr-met oncogene breakpoint. Mol Cell Biol. 1987 Feb;7(2):921–924. doi: 10.1128/mcb.7.2.921. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fainstein E., Marcelle C., Rosner A., Canaani E., Gale R. P., Dreazen O., Smith S. D., Croce C. M. A new fused transcript in Philadelphia chromosome positive acute lymphocytic leukaemia. 1987 Nov 26-Dec 2Nature. 330(6146):386–388. doi: 10.1038/330386a0. [DOI] [PubMed] [Google Scholar]
  9. Groffen J., Stephenson J. R., Heisterkamp N., de Klein A., Bartram C. R., Grosveld G. Philadelphia chromosomal breakpoints are clustered within a limited region, bcr, on chromosome 22. Cell. 1984 Jan;36(1):93–99. doi: 10.1016/0092-8674(84)90077-1. [DOI] [PubMed] [Google Scholar]
  10. Grosveld G., Verwoerd T., van Agthoven T., de Klein A., Ramachandran K. L., Heisterkamp N., Stam K., Groffen J. The chronic myelocytic cell line K562 contains a breakpoint in bcr and produces a chimeric bcr/c-abl transcript. Mol Cell Biol. 1986 Feb;6(2):607–616. doi: 10.1128/mcb.6.2.607. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Haltiner M., Kempe T., Tjian R. A novel strategy for constructing clustered point mutations. Nucleic Acids Res. 1985 Feb 11;13(3):1015–1025. doi: 10.1093/nar/13.3.1015. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Heisterkamp N., Stam K., Groffen J., de Klein A., Grosveld G. Structural organization of the bcr gene and its role in the Ph' translocation. 1985 Jun 27-Jul 3Nature. 315(6022):758–761. doi: 10.1038/315758a0. [DOI] [PubMed] [Google Scholar]
  13. Heisterkamp N., Stephenson J. R., Groffen J., Hansen P. F., de Klein A., Bartram C. R., Grosveld G. Localization of the c-ab1 oncogene adjacent to a translocation break point in chronic myelocytic leukaemia. Nature. 1983 Nov 17;306(5940):239–242. doi: 10.1038/306239a0. [DOI] [PubMed] [Google Scholar]
  14. Hermans A., Heisterkamp N., von Linden M., van Baal S., Meijer D., van der Plas D., Wiedemann L. M., Groffen J., Bootsma D., Grosveld G. Unique fusion of bcr and c-abl genes in Philadelphia chromosome positive acute lymphoblastic leukemia. Cell. 1987 Oct 9;51(1):33–40. doi: 10.1016/0092-8674(87)90007-9. [DOI] [PubMed] [Google Scholar]
  15. Hyrien O., Debatisse M., Buttin G., de Saint Vincent B. R. The multicopy appearance of a large inverted duplication and the sequence at the inversion joint suggest a new model for gene amplification. EMBO J. 1988 Feb;7(2):407–417. doi: 10.1002/j.1460-2075.1988.tb02828.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kloetzer W., Kurzrock R., Smith L., Talpaz M., Spiller M., Gutterman J., Arlinghaus R. The human cellular abl gene product in the chronic myelogenous leukemia cell line K562 has an associated tyrosine protein kinase activity. Virology. 1985 Jan 30;140(2):230–238. doi: 10.1016/0042-6822(85)90361-7. [DOI] [PubMed] [Google Scholar]
  17. Koeffler H. P., Golde D. W. Acute myelogenous leukemia: a human cell line responsive to colony-stimulating activity. Science. 1978 Jun 9;200(4346):1153–1154. doi: 10.1126/science.306682. [DOI] [PubMed] [Google Scholar]
  18. Kurzrock R., Shtalrid M., Romero P., Kloetzer W. S., Talpas M., Trujillo J. M., Blick M., Beran M., Gutterman J. U. A novel c-abl protein product in Philadelphia-positive acute lymphoblastic leukaemia. Nature. 1987 Feb 12;325(6105):631–635. doi: 10.1038/325631a0. [DOI] [PubMed] [Google Scholar]
  19. Lehrman M. A., Schneider W. J., Südhof T. C., Brown M. S., Goldstein J. L., Russell D. W. Mutation in LDL receptor: Alu-Alu recombination deletes exons encoding transmembrane and cytoplasmic domains. Science. 1985 Jan 11;227(4683):140–146. doi: 10.1126/science.3155573. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Nalbantoglu J., Hartley D., Phear G., Tear G., Meuth M. Spontaneous deletion formation at the aprt locus of hamster cells: the presence of short sequence homologies and dyad symmetries at deletion termini. EMBO J. 1986 Jun;5(6):1199–1204. doi: 10.1002/j.1460-2075.1986.tb04347.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Nicholls R. D., Fischel-Ghodsian N., Higgs D. R. Recombination at the human alpha-globin gene cluster: sequence features and topological constraints. Cell. 1987 May 8;49(3):369–378. doi: 10.1016/0092-8674(87)90289-3. [DOI] [PubMed] [Google Scholar]
  22. Panganiban A. T. Retroviral DNA integration. Cell. 1985 Aug;42(1):5–6. doi: 10.1016/s0092-8674(85)80092-1. [DOI] [PubMed] [Google Scholar]
  23. Piccoli S. P., Caimi P. G., Cole M. D. A conserved sequence at c-myc oncogene chromosomal translocation breakpoints in plasmacytomas. 1984 Jul 26-Aug 1Nature. 310(5975):327–330. doi: 10.1038/310327a0. [DOI] [PubMed] [Google Scholar]
  24. Rabbitts T. H., Baer R., Buluwela L., Mengle-Gaw L., Taylor A. M., Rabbitts P. H. Molecular genetics of antigen receptors and associated chromosomal abnormalities in human leukemias. Cold Spring Harb Symp Quant Biol. 1986;51(Pt 2):923–930. doi: 10.1101/sqb.1986.051.01.105. [DOI] [PubMed] [Google Scholar]
  25. Ribeiro R. C., Abromowitch M., Raimondi S. C., Murphy S. B., Behm F., Williams D. L. Clinical and biologic hallmarks of the Philadelphia chromosome in childhood acute lymphoblastic leukemia. Blood. 1987 Oct;70(4):948–953. [PubMed] [Google Scholar]
  26. Rogers J. H. The origin and evolution of retroposons. Int Rev Cytol. 1985;93:187–279. doi: 10.1016/s0074-7696(08)61375-3. [DOI] [PubMed] [Google Scholar]
  27. Roth D. B., Wilson J. H. Nonhomologous recombination in mammalian cells: role for short sequence homologies in the joining reaction. Mol Cell Biol. 1986 Dec;6(12):4295–4304. doi: 10.1128/mcb.6.12.4295. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Rouyer F., Simmler M. C., Page D. C., Weissenbach J. A sex chromosome rearrangement in a human XX male caused by Alu-Alu recombination. Cell. 1987 Nov 6;51(3):417–425. doi: 10.1016/0092-8674(87)90637-4. [DOI] [PubMed] [Google Scholar]
  29. Rowley J. D. Letter: A new consistent chromosomal abnormality in chronic myelogenous leukaemia identified by quinacrine fluorescence and Giemsa staining. Nature. 1973 Jun 1;243(5405):290–293. doi: 10.1038/243290a0. [DOI] [PubMed] [Google Scholar]
  30. Rubin C. M., Carrino J. J., Dickler M. N., Leibowitz D., Smith S. D., Westbrook C. A. Heterogeneity of genomic fusion of BCR and ABL in Philadelphia chromosome-positive acute lymphoblastic leukemia. Proc Natl Acad Sci U S A. 1988 Apr;85(8):2795–2799. doi: 10.1073/pnas.85.8.2795. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. 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]
  32. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Schmid C. W., Jelinek W. R. The Alu family of dispersed repetitive sequences. Science. 1982 Jun 4;216(4550):1065–1070. doi: 10.1126/science.6281889. [DOI] [PubMed] [Google Scholar]
  34. Shtivelman E., Lifshitz B., Gale R. P., Canaani E. Fused transcript of abl and bcr genes in chronic myelogenous leukaemia. Nature. 1985 Jun 13;315(6020):550–554. doi: 10.1038/315550a0. [DOI] [PubMed] [Google Scholar]
  35. Vieira J., Messing J. The pUC plasmids, an M13mp7-derived system for insertion mutagenesis and sequencing with synthetic universal primers. Gene. 1982 Oct;19(3):259–268. doi: 10.1016/0378-1119(82)90015-4. [DOI] [PubMed] [Google Scholar]
  36. Walker L. C., Ganesan T. S., Dhut S., Gibbons B., Lister T. A., Rothbard J., Young B. D. Novel chimaeric protein expressed in Philadelphia positive acute lymphoblastic leukaemia. 1987 Oct 29-Nov 4Nature. 329(6142):851–853. doi: 10.1038/329851a0. [DOI] [PubMed] [Google Scholar]
  37. Yanisch-Perron C., Vieira J., Messing J. Improved M13 phage cloning vectors and host strains: nucleotide sequences of the M13mp18 and pUC19 vectors. Gene. 1985;33(1):103–119. doi: 10.1016/0378-1119(85)90120-9. [DOI] [PubMed] [Google Scholar]
  38. Zech L., Gahrton G., Hammarström L., Juliusson G., Mellstedt H., Robèrt K. H., Smith C. I. Inversion of chromosome 14 marks human T-cell chronic lymphocytic leukaemia. 1984 Apr 26-May 2Nature. 308(5962):858–860. doi: 10.1038/308858a0. [DOI] [PubMed] [Google Scholar]
  39. de Klein A., van Agthoven T., Groffen C., Heisterkamp N., Groffen J., Grosveld G. Molecular analysis of both translocation products of a Philadelphia-positive CML patient. Nucleic Acids Res. 1986 Sep 11;14(17):7071–7082. doi: 10.1093/nar/14.17.7071. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. van der Feltz M. J., Shivji M. K., Grosveld G., Wiedemann L. M. Characterization of the translocation breakpoint in a patient with Philadelphia positive, bcr negative acute lymphoblastic leukaemia. Oncogene. 1988 Aug;3(2):215–219. [PubMed] [Google Scholar]

Articles from Nucleic Acids Research are provided here courtesy of Oxford University Press

RESOURCES