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. 1989 Oct 11;17(19):7631–7642. doi: 10.1093/nar/17.19.7631

Structural alterations of the BCR and ABL genes in Ph1 positive acute leukemias with rearrangements in the BCR gene first intron: further evidence implicating Alu sequences in the chromosome translocation.

S J Chen 1, Z Chen 1, M P Font 1, L d'Auriol 1, C J Larsen 1, R Berger 1
PMCID: PMC334872  PMID: 2678002

Abstract

In the Philadelphia positive bcr negative acute leukemias (Ph1+bcr- AL), the chromosomal breakpoints on chromosome 22 have been shown clustered within 10.8kb (bcr2) and 5kb (bcr3) fragments of the first intron of the BCR gene. We previously reported that the breakpoints were localized in Alu repeats on chromosomes 9 and 22 in a Ph1+bcr- acute lymphoblastic leukemia with a rearrangement involving bcr2. Molecular data of two other Ph1 translocations, one a Ph1+bcr- acute myeloblastic leukemia in the bcr2 region, and the other an acute lymphoblastic leukemia in the bcr3 region are presented. In the former, the breakpoints on chromosomes 9 and 22 are localized in Alu repeats, in regions with two inverted Alu sequences, as in our previously reported case. In the second leukemia, the breakpoints are not located in Alu sequences, but such repeats are found in their vicinity. The implications of these findings are discussed.

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Selected References

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

  1. 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]
  2. Britten R. J., Baron W. F., Stout D. B., Davidson E. H. Sources and evolution of human Alu repeated sequences. Proc Natl Acad Sci U S A. 1988 Jul;85(13):4770–4774. doi: 10.1073/pnas.85.13.4770. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chen S. J., Chen Z., Grausz J. D., Hillion J., d'Auriol L., Flandrin G., Larsen C. J., Berger R. Molecular cloning of a 5' segment of the genomic phl gene defines a new breakpoint cluster region (bcr2) in Philadelphia-positive acute leukemias. Leukemia. 1988 Oct;2(10):634–641. [PubMed] [Google Scholar]
  4. Chen S. J., Chen Z., Hillion J., Grausz D., Loiseau P., Flandrin G., Berger R. Ph1-positive, bcr-negative acute leukemias: clustering of breakpoints on chromosome 22 in the 3' end of the BCR gene first intron. Blood. 1989 Apr;73(5):1312–1315. [PubMed] [Google Scholar]
  5. Chen S. J., Chen Z., d'Auriol L., Le Coniat M., Grausz D., Berger R. Ph1+bcr- acute leukemias: implication of Alu sequences in a chromosomal translocation occurring in the new cluster region within the BCR gene. Oncogene. 1989 Feb;4(2):195–202. [PubMed] [Google Scholar]
  6. Chen S. J., Flandrin G., Daniel M. T., Valensi F., Baranger L., Grausz D., Bernheim A., Chen Z., Sigaux F., Berger R. Philadelphia-positive acute leukemia: lineage promiscuity and inconsistently rearranged breakpoint cluster region. Leukemia. 1988 May;2(5):261–273. [PubMed] [Google Scholar]
  7. Chen Z., Font M. P., Loiseau P., Bories J. C., Degos L., Lefranc M. P., Sigaux F. The human T-cell V gamma gene locus: cloning of new segments and study of V gamma rearrangements in neoplastic T and B cells. Blood. 1988 Aug;72(2):776–783. [PubMed] [Google Scholar]
  8. Clark S. S., Crist W. M., Witte O. N. Molecular pathogenesis of Ph-positive leukemias. Annu Rev Med. 1989;40:113–122. doi: 10.1146/annurev.me.40.020189.000553. [DOI] [PubMed] [Google Scholar]
  9. Denny C. T., Shah N. P., Ogden S., Willman C., McConnell T., Crist W., Carroll A., Witte O. N. Localization of preferential sites of rearrangement within the BCR gene in Philadelphia chromosome-positive acute lymphoblastic leukemia. Proc Natl Acad Sci U S A. 1989 Jun;86(11):4254–4258. doi: 10.1073/pnas.86.11.4254. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. 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]
  11. Heisterkamp N., Jenkins R., Thibodeau S., Testa J. R., Weinberg K., Groffen J. The bcr gene in Philadelphia chromosome positive acute lymphoblastic leukemia. Blood. 1989 Apr;73(5):1307–1311. [PubMed] [Google Scholar]
  12. Heisterkamp N., Knoppel E., Groffen J. The first BCR gene intron contains breakpoints in Philadelphia chromosome positive leukemia. Nucleic Acids Res. 1988 Nov 11;16(21):10069–10081. doi: 10.1093/nar/16.21.10069. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. 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]
  14. Hirosawa S., Aoki N., Matsushime H., Shibuya M. Undetectable bcr-abl rearrangements in some CML patients are due to a deletion mutation in the bcr gene. Am J Hematol. 1988 May;28(1):33–36. doi: 10.1002/ajh.2830280107. [DOI] [PubMed] [Google Scholar]
  15. Kurzrock R., Gutterman J. U., Talpaz M. The molecular genetics of Philadelphia chromosome-positive leukemias. N Engl J Med. 1988 Oct 13;319(15):990–998. doi: 10.1056/NEJM198810133191506. [DOI] [PubMed] [Google Scholar]
  16. Popenoe D. W., Schaefer-Rego K., Mears J. G., Bank A., Leibowitz D. Frequent and extensive deletion during the 9,22 translocation in CML. Blood. 1986 Nov;68(5):1123–1128. [PubMed] [Google Scholar]
  17. Rogers J. Oncogene chromosome breakpoints and alu sequences. Nature. 1985 Oct 10;317(6037):559–559. doi: 10.1038/317559a0. [DOI] [PubMed] [Google Scholar]
  18. Rogers J. Oncogene chromosome breakpoints and alu sequences. Nature. 1985 Oct 10;317(6037):559–559. doi: 10.1038/317559a0. [DOI] [PubMed] [Google Scholar]
  19. 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]
  20. Shtalrid M., Talpaz M., Kurzrock R., Kantarjian H., Trujillo J., Gutterman J., Yoffe G., Blick M. Analysis of breakpoints within the bcr gene and their correlation with the clinical course of Philadelphia-positive chronic myelogenous leukemia. Blood. 1988 Aug;72(2):485–490. [PubMed] [Google Scholar]
  21. Tsujimoto Y., Gorham J., Cossman J., Jaffe E., Croce C. M. The t(14;18) chromosome translocations involved in B-cell neoplasms result from mistakes in VDJ joining. Science. 1985 Sep 27;229(4720):1390–1393. doi: 10.1126/science.3929382. [DOI] [PubMed] [Google Scholar]
  22. Westbrook C. A., Rubin C. M., Carrino J. J., Le Beau M. M., Bernards A., Rowley J. D. Long-range mapping of the Philadelphia chromosome by pulsed-field gel electrophoresis. Blood. 1988 Mar;71(3):697–702. [PubMed] [Google Scholar]
  23. 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]
  24. van der Feltz M. J., Shivji M. K., Allen P. B., Heisterkamp N., Groffen J., Wiedemann L. M. 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. Nucleic Acids Res. 1989 Jan 11;17(1):1–10. doi: 10.1093/nar/17.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]

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