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Molecular Pathology : MP logoLink to Molecular Pathology : MP
. 1998 Dec;51(6):333–338. doi: 10.1136/mp.51.6.333

Detection of t(14;18) carrying cells in bone marrow and peripheral blood from patients affected by non-lymphoid diseases.

O Rauzy 1, S Galoin 1, J J Chale 1, D Adoue 1, J L Albarede 1, G Delsol 1, T al Saati 1
PMCID: PMC395660  PMID: 10193514

Abstract

AIMS/BACKGROUND: To assess the presence of bcl-2/JH rearrangements in bone marrow and peripheral blood lymphocytes from patients affected by diseases other than malignant lymphomas. The t(14;18) (q32;q21) translocation, which juxtaposes the bcl-2 oncogene on chromosome 18 and the JH segment of the immunoglobulin heavy chain (IgH) genes on chromosome 14, is found frequently in follicular lymphomas. METHODS: A sensitive semi-nested polymerase chain reaction (PCR) was used to detect t(14;18) translocation in bone marrow aspirates and peripheral blood lymphocytes from 48 patients. In 137 additional individuals peripheral blood lymphocytes only were tested. RESULTS: Cells carrying bcl-2/JH rearrangements were detected in about a quarter of the bone marrow samples and half of the peripheral blood lymphocyte samples. In seven patients, t(14;18) positive cells were found in both the bone marrow and peripheral blood lymphocyte samples. The size of the PCR products and bcl-2/JH DNA sequence analysis showed that the same t(14;18) carrying clone was present in the bone marrow and the corresponding peripheral blood lymphocyte samples in three of these seven patients. Some patients had more than one bcl-2/JH rearrangement. There was no significant correlation between age and the translocation incidence. Cells carrying the t(14;18) translocation were present in peripheral blood lymphocyte samples with a similar incidence--between 47% and 52% in all age groups from 20 to 79 years. Patients older than 80 years had a lower (37%) but not significantly different incidence. CONCLUSIONS: These findings suggest that patients affected by non-lymphoid diseases may have several t(14;18) carrying cells and some of them undergo a clonal expansion. Whether individuals with t(14;18) positive cells are at a higher risk of lymphoid malignancies remains unanswered and further epidemiological studies are required.

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Selected References

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  1. Bell D. A., Liu Y., Cortopassi G. A. Occurrence of bcl-2 oncogene translocation with increased frequency in the peripheral blood of heavy smokers. J Natl Cancer Inst. 1995 Feb 1;87(3):223–224. doi: 10.1093/jnci/87.3.223. [DOI] [PubMed] [Google Scholar]
  2. Berinstein N. L., Jamal H. H., Kuzniar B., Klock R. J., Reis M. D. Sensitive and reproducible detection of occult disease in patients with follicular lymphoma by PCR amplification of t(14;18) both pre- and post-treatment. Leukemia. 1993 Jan;7(1):113–119. [PubMed] [Google Scholar]
  3. Bonner T. I., Kerby S. B., Sutrave P., Gunnell M. A., Mark G., Rapp U. R. Structure and biological activity of human homologs of the raf/mil oncogene. Mol Cell Biol. 1985 Jun;5(6):1400–1407. doi: 10.1128/mcb.5.6.1400. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cleary M. L., Sklar J. Nucleotide sequence of a t(14;18) chromosomal breakpoint in follicular lymphoma and demonstration of a breakpoint-cluster region near a transcriptionally active locus on chromosome 18. Proc Natl Acad Sci U S A. 1985 Nov;82(21):7439–7443. doi: 10.1073/pnas.82.21.7439. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Crescenzi M., Seto M., Herzig G. P., Weiss P. D., Griffith R. C., Korsmeyer S. J. Thermostable DNA polymerase chain amplification of t(14;18) chromosome breakpoints and detection of minimal residual disease. Proc Natl Acad Sci U S A. 1988 Jul;85(13):4869–4873. doi: 10.1073/pnas.85.13.4869. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Dölken G., Illerhaus G., Hirt C., Mertelsmann R. BCL-2/JH rearrangements in circulating B cells of healthy blood donors and patients with nonmalignant diseases. J Clin Oncol. 1996 Apr;14(4):1333–1344. doi: 10.1200/JCO.1996.14.4.1333. [DOI] [PubMed] [Google Scholar]
  7. Fuscoe J. C., Setzer R. W., Collard D. D., Moore M. M. Quantification of t(14;18) in the lymphocytes of healthy adult humans as a possible biomarker for environmental exposures to carcinogens. Carcinogenesis. 1996 May;17(5):1013–1020. doi: 10.1093/carcin/17.5.1013. [DOI] [PubMed] [Google Scholar]
  8. Galoin S., al Saati T., Schlaifer D., Huynh A., Attal M., Delsol G. Oligonucleotide clonospecific probes directed against the junctional sequence of t(14;18): a new tool for the assessment of minimal residual disease in follicular lymphomas. Br J Haematol. 1996 Sep;94(4):676–684. doi: 10.1046/j.1365-2141.1996.7062323.x. [DOI] [PubMed] [Google Scholar]
  9. Gravel S., Delsol G., Al Saati T. Single-cell analysis of the t(14;18)(q32;q21) chromosomal translocation in Hodgkin's disease demonstrates the absence of this translocation in neoplastic Hodgkin and Reed-Sternberg cells. Blood. 1998 Apr 15;91(8):2866–2874. [PubMed] [Google Scholar]
  10. Gribben J. G., Neuberg D., Freedman A. S., Gimmi C. D., Pesek K. W., Barber M., Saporito L., Woo S. D., Coral F., Spector N. Detection by polymerase chain reaction of residual cells with the bcl-2 translocation is associated with increased risk of relapse after autologous bone marrow transplantation for B-cell lymphoma. Blood. 1993 Jun 15;81(12):3449–3457. [PubMed] [Google Scholar]
  11. Gribben J. G., Schultze J. L. The detection of minimal residual disease: implications for bone marrow transplantation. Cancer Treat Res. 1997;77:99–120. doi: 10.1007/978-1-4615-6349-5_5. [DOI] [PubMed] [Google Scholar]
  12. Harris N. L., Jaffe E. S., Stein H., Banks P. M., Chan J. K., Cleary M. L., Delsol G., De Wolf-Peeters C., Falini B., Gatter K. C. A revised European-American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group. Blood. 1994 Sep 1;84(5):1361–1392. [PubMed] [Google Scholar]
  13. Ji W., Qu G. Z., Ye P., Zhang X. Y., Halabi S., Ehrlich M. Frequent detection of bcl-2/JH translocations in human blood and organ samples by a quantitative polymerase chain reaction assay. Cancer Res. 1995 Jul 1;55(13):2876–2882. [PubMed] [Google Scholar]
  14. Kneba M., Eick S., Herbst H., Willigeroth S., Pott C., Bolz I., Bergholz M., Neumann C., Stein H., Krieger G. Frequency and structure of t(14;18) major breakpoint regions in non-Hodgkin's lymphomas typed according to the Kiel classification: analysis by direct DNA sequencing. Cancer Res. 1991 Jun 15;51(12):3243–3250. [PubMed] [Google Scholar]
  15. Knutsen T. Cytogenetic mechanisms in the pathogenesis and progression of follicular lymphoma. Cancer Surv. 1997;30:163–192. [PubMed] [Google Scholar]
  16. Kwok S., Higuchi R. Avoiding false positives with PCR. Nature. 1989 May 18;339(6221):237–238. doi: 10.1038/339237a0. [DOI] [PubMed] [Google Scholar]
  17. Lee M. S., Chang K. S., Cabanillas F., Freireich E. J., Trujillo J. M., Stass S. A. Detection of minimal residual cells carrying the t(14;18) by DNA sequence amplification. Science. 1987 Jul 10;237(4811):175–178. doi: 10.1126/science.3110950. [DOI] [PubMed] [Google Scholar]
  18. Limpens J., Stad R., Vos C., de Vlaam C., de Jong D., van Ommen G. J., Schuuring E., Kluin P. M. Lymphoma-associated translocation t(14;18) in blood B cells of normal individuals. Blood. 1995 May 1;85(9):2528–2536. [PubMed] [Google Scholar]
  19. Limpens J., de Jong D., van Krieken J. H., Price C. G., Young B. D., van Ommen G. J., Kluin P. M. Bcl-2/JH rearrangements in benign lymphoid tissues with follicular hyperplasia. Oncogene. 1991 Dec;6(12):2271–2276. [PubMed] [Google Scholar]
  20. Liu Y., Hernandez A. M., Shibata D., Cortopassi G. A. BCL2 translocation frequency rises with age in humans. Proc Natl Acad Sci U S A. 1994 Sep 13;91(19):8910–8914. doi: 10.1073/pnas.91.19.8910. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. McDonnell T. J., Korsmeyer S. J. Progression from lymphoid hyperplasia to high-grade malignant lymphoma in mice transgenic for the t(14; 18). Nature. 1991 Jan 17;349(6306):254–256. doi: 10.1038/349254a0. [DOI] [PubMed] [Google Scholar]
  22. Ravetch J. V., Siebenlist U., Korsmeyer S., Waldmann T., Leder P. Structure of the human immunoglobulin mu locus: characterization of embryonic and rearranged J and D genes. Cell. 1981 Dec;27(3 Pt 2):583–591. doi: 10.1016/0092-8674(81)90400-1. [DOI] [PubMed] [Google Scholar]
  23. 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]
  24. Soubeyran P., Cabanillas F., Lee M. S. Analysis of the expression of the hybrid gene bcl-2/IgH in follicular lymphomas. Blood. 1993 Jan 1;81(1):122–127. [PubMed] [Google Scholar]
  25. 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]
  26. Wyatt R. T., Rudders R. A., Zelenetz A., Delellis R. A., Krontiris T. G. BCL2 oncogene translocation is mediated by a chi-like consensus. J Exp Med. 1992 Jun 1;175(6):1575–1588. doi: 10.1084/jem.175.6.1575. [DOI] [PMC free article] [PubMed] [Google Scholar]

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