Skip to main content
British Journal of Cancer logoLink to British Journal of Cancer
. 1993 May;67(5):922–925. doi: 10.1038/bjc.1993.171

Detection of bcl-2/JH rearrangement in follicular and diffuse lymphoma: concordant results of peripheral blood and bone marrow analysis at diagnosis.

R Yuan 1, P Dowling 1, E Zucca 1, H Diggelmann 1, F Cavalli 1
PMCID: PMC1968466  PMID: 8494725

Abstract

The capacity to detect t(14;18) breakpoints in non-Hodgkin's lymphoma (NHL) peripheral blood and bone marrow was studied by DNA PCR. We studied 33 patients with follicular lymphoma (FL) (Working Formulation subtypes B, C, D) and 38 patients with intermediate-grade NHL (subtypes F, G). In the FL subgroup, 86% of the morphologically-positive bone marrow patients had amplifiable t(14;18) breakpoints by PCR. Remarkably, of 19 FL patients with 'negative' bone marrows, 11 (58%) were PCR-positive. In addition, half of the early clinical stage patients (I and II) had detectable breakpoints in their bone marrow DNA. Samples from NHL patients with intermediate-grade disease exhibit the same phenomena but at a considerably lower frequency. Paired peripheral blood and bone marrow samples were available at diagnosis in a subset of 56 patients. The concordance between bone marrow and peripheral blood PCR findings was high, with peripheral blood of 55/56 showing the same PCR results as the corresponding bone marrow.

Full text

PDF

Images in this article

Selected References

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

  1. Aisenberg A. C., Wilkes B. M., Jacobson J. O. The bcl-2 gene is rearranged in many diffuse B-cell lymphomas. Blood. 1988 Apr;71(4):969–972. [PubMed] [Google Scholar]
  2. Bakhshi A., Jensen J. P., Goldman P., Wright J. J., McBride O. W., Epstein A. L., Korsmeyer S. J. Cloning the chromosomal breakpoint of t(14;18) human lymphomas: clustering around JH on chromosome 14 and near a transcriptional unit on 18. Cell. 1985 Jul;41(3):899–906. doi: 10.1016/s0092-8674(85)80070-2. [DOI] [PubMed] [Google Scholar]
  3. Cleary M. L., Galili N., Sklar J. Detection of a second t(14;18) breakpoint cluster region in human follicular lymphomas. J Exp Med. 1986 Jul 1;164(1):315–320. doi: 10.1084/jem.164.1.315. [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. Cleary M. L., Smith S. D., Sklar J. Cloning and structural analysis of cDNAs for bcl-2 and a hybrid bcl-2/immunoglobulin transcript resulting from the t(14;18) translocation. Cell. 1986 Oct 10;47(1):19–28. doi: 10.1016/0092-8674(86)90362-4. [DOI] [PubMed] [Google Scholar]
  6. Cotter F., Price C., Zucca E., Young B. D. Direct sequence analysis of the 14q+ and 18q- chromosome junctions in follicular lymphoma. Blood. 1990 Jul 1;76(1):131–135. [PubMed] [Google Scholar]
  7. 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]
  8. Dick F., Bloomfield C. D., Brunning R. D. Incidence cytology, and histopathology of non-Hodgkin's lymphomas in the bone marrow. Cancer. 1974 May;33(5):1382–1398. doi: 10.1002/1097-0142(197405)33:5<1382::aid-cncr2820330525>3.0.co;2-2. [DOI] [PubMed] [Google Scholar]
  9. Gribben J. G., Freedman A. s., Woo S. D., Blake K., Shu R. S., Freeman G., Longtine J. A., Pinkus G. S., Nadler L. M. All advanced stage non-Hodgkin's lymphomas with a polymerase chain reaction amplifiable breakpoint of bcl-2 have residual cells containing the bcl-2 rearrangement at evaluation and after treatment. Blood. 1991 Dec 15;78(12):3275–3280. [PubMed] [Google Scholar]
  10. Hickish T. F., Purvies H., Mansi J., Soukop M., Cunningham D. Molecular monitoring of low grade non-Hodgkin's lymphoma by gene amplification. Br J Cancer. 1991 Dec;64(6):1161–1163. doi: 10.1038/bjc.1991.482. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hockenbery D., Nuñez G., Milliman C., Schreiber R. D., Korsmeyer S. J. Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death. Nature. 1990 Nov 22;348(6299):334–336. doi: 10.1038/348334a0. [DOI] [PubMed] [Google Scholar]
  12. Kluin-Nelemans H. C., Limpens J., Meerabux J., Beverstock G. C., Jansen J. H., de Jong D., Kluin P. M. A new non-Hodgkin's B-cell line (DoHH2) with a chromosomal translocation t(14;18)(q32;q21). Leukemia. 1991 Mar;5(3):221–224. [PubMed] [Google Scholar]
  13. 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]
  14. Lambrechts A. C., de Ruiter P. E., Dorssers L. C., van 't Veer M. B. Detection of residual disease in translocation (14;18) positive non-Hodgkin's lymphoma, using the polymerase chain reaction: a comparison with conventional staging methods. Leukemia. 1992 Jan;6(1):29–34. [PubMed] [Google Scholar]
  15. Lee M. S., Blick M. B., Pathak S., Trujillo J. M., Butler J. J., Katz R. L., McLaughlin P., Hagemeister F. B., Velasquez W. S., Goodacre A. The gene located at chromosome 18 band q21 is rearranged in uncultured diffuse lymphomas as well as follicular lymphomas. Blood. 1987 Jul;70(1):90–95. [PubMed] [Google Scholar]
  16. 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]
  17. McDonnell T. J., Deane N., Platt F. M., Nunez G., Jaeger U., McKearn J. P., Korsmeyer S. J. bcl-2-immunoglobulin transgenic mice demonstrate extended B cell survival and follicular lymphoproliferation. Cell. 1989 Apr 7;57(1):79–88. doi: 10.1016/0092-8674(89)90174-8. [DOI] [PubMed] [Google Scholar]
  18. Ngan B. Y., Chen-Levy Z., Weiss L. M., Warnke R. A., Cleary M. L. Expression in non-Hodgkin's lymphoma of the bcl-2 protein associated with the t(14;18) chromosomal translocation. N Engl J Med. 1988 Jun 23;318(25):1638–1644. doi: 10.1056/NEJM198806233182502. [DOI] [PubMed] [Google Scholar]
  19. Ngan B. Y., Nourse J., Cleary M. L. Detection of chromosomal translocation t(14;18) within the minor cluster region of bcl-2 by polymerase chain reaction and direct genomic sequencing of the enzymatically amplified DNA in follicular lymphomas. Blood. 1989 May 15;73(7):1759–1762. [PubMed] [Google Scholar]
  20. Pezzella F., Jones M., Ralfkiaer E., Ersbøll J., Gatter K. C., Mason D. Y. Evaluation of bcl-2 protein expression and 14;18 translocation as prognostic markers in follicular lymphoma. Br J Cancer. 1992 Jan;65(1):87–89. doi: 10.1038/bjc.1992.16. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Price C. G., Meerabux J., Murtagh S., Cotter F. E., Rohatiner A. Z., Young B. D., Lister T. A. The significance of circulating cells carrying t(14;18) in long remission from follicular lymphoma. J Clin Oncol. 1991 Sep;9(9):1527–1532. doi: 10.1200/JCO.1991.9.9.1527. [DOI] [PubMed] [Google Scholar]
  22. Rosenberg S. A. Bone marrow involvement in the non-Hodgkin's lymphomata. Br J Cancer Suppl. 1975 Mar;2:261–264. [PMC free article] [PubMed] [Google Scholar]
  23. Simon R., Durrleman S., Hoppe R. T., Bonadonna G., Bloomfield C. D., Rudders R. A., Cheson B. D., Berard C. W. The Non-Hodgkin Lymphoma Pathologic Classification Project. Long-term follow-up of 1153 patients with non-Hodgkin lymphomas. Ann Intern Med. 1988 Dec 15;109(12):939–945. doi: 10.7326/0003-4819-109-12-939. [DOI] [PubMed] [Google Scholar]
  24. Stein R. S., Ultmann J. E., Byrne G. E., Jr, Moran E. M., Golomb H. M., Oetzel N. Bone marrow involvement in non-Hodgkin's lymphoma: implications for staging and therapy. Cancer. 1976 Feb;37(2):629–636. doi: 10.1002/1097-0142(197602)37:2<629::aid-cncr2820370204>3.0.co;2-k. [DOI] [PubMed] [Google Scholar]
  25. Stetlet-Stevenson M., Raffeld M., Cohen P., Cossman J. Detection of occult follicular lymphoma by specific DNA amplification. Blood. 1988 Nov;72(5):1822–1825. [PubMed] [Google Scholar]
  26. Tsujimoto Y., Cossman J., Jaffe E., Croce C. M. Involvement of the bcl-2 gene in human follicular lymphoma. Science. 1985 Jun 21;228(4706):1440–1443. doi: 10.1126/science.3874430. [DOI] [PubMed] [Google Scholar]
  27. 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. 1984 Nov 30;226(4678):1097–1099. doi: 10.1126/science.6093263. [DOI] [PubMed] [Google Scholar]
  28. Weiss L. M., Warnke R. A., Sklar J., Cleary M. L. Molecular analysis of the t(14;18) chromosomal translocation in malignant lymphomas. N Engl J Med. 1987 Nov 5;317(19):1185–1189. doi: 10.1056/NEJM198711053171904. [DOI] [PubMed] [Google Scholar]
  29. Yunis J. J., Mayer M. G., Arnesen M. A., Aeppli D. P., Oken M. M., Frizzera G. bcl-2 and other genomic alterations in the prognosis of large-cell lymphoma. N Engl J Med. 1989 Apr 20;320(16):1047–1054. doi: 10.1056/NEJM198904203201605. [DOI] [PubMed] [Google Scholar]
  30. Yunis J. J., Oken M. M., Kaplan M. E., Ensrud K. M., Howe R. R., Theologides A. Distinctive chromosomal abnormalities in histologic subtypes of non-Hodgkin's lymphoma. N Engl J Med. 1982 Nov 11;307(20):1231–1236. doi: 10.1056/NEJM198211113072002. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES