Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1995 Jul 3;92(14):6577–6581. doi: 10.1073/pnas.92.14.6577

Persistence of immunoglobulin heavy chain/c-myc recombination-positive lymphocyte clones in the blood of human immunodeficiency virus-infected homosexual men.

J R Müller 1, S Janz 1, J J Goedert 1, M Potter 1, C S Rabkin 1
PMCID: PMC41561  PMID: 7604036

Abstract

We studied blood lymphocytes of human immunodeficiency virus (HIV)-seropositive and -negative homosexual men for the presence of T(8;14) translocations that recombine c-myc and immunoglobulin heavy-chain (IgH) mu/IgH alpha switch regions. Clones with T(8;14) translocations were detected in 10.5% (12/114) of the HIV-positive and in 2.0% of the 99 uninfected patients. The majority of recombinations were found at a single time point only. Four patients, however, harbored multiple (up to four) and persistent (up to 9 years) translocation-positive cell clones. No correlation between the presence of these aberrant lymphocytes and a later lymphoma could be established. The exon 1/intron 1 region of the recombined c-myc was investigated for the presence of point mutations and these were found in the nonpersistent clones. Additional alterations detected in these clones included duplications and a deletion in the c-myc gene. The pattern of base substitution indicates that they were introduced after the translocation event.

Full text

PDF
6577

Images in this article

6581Fig. 3
on p.6581

Selected References

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

  1. Ballerini P., Gaidano G., Gong J. Z., Tassi V., Saglio G., Knowles D. M., Dalla-Favera R. Multiple genetic lesions in acquired immunodeficiency syndrome-related non-Hodgkin's lymphoma. Blood. 1993 Jan 1;81(1):166–176. [PubMed] [Google Scholar]
  2. Beral V., Peterman T., Berkelman R., Jaffe H. AIDS-associated non-Hodgkin lymphoma. Lancet. 1991 Apr 6;337(8745):805–809. doi: 10.1016/0140-6736(91)92513-2. [DOI] [PubMed] [Google Scholar]
  3. Betz A. G., Rada C., Pannell R., Milstein C., Neuberger M. S. Passenger transgenes reveal intrinsic specificity of the antibody hypermutation mechanism: clustering, polarity, and specific hot spots. Proc Natl Acad Sci U S A. 1993 Mar 15;90(6):2385–2388. doi: 10.1073/pnas.90.6.2385. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bhatia K., Spangler G., Gaidano G., Hamdy N., Dalla-Favera R., Magrath I. Mutations in the coding region of c-myc occur frequently in acquired immunodeficiency syndrome-associated lymphomas. Blood. 1994 Aug 1;84(3):883–888. [PubMed] [Google Scholar]
  5. Breen E. C., Rezai A. R., Nakajima K., Beall G. N., Mitsuyasu R. T., Hirano T., Kishimoto T., Martinez-Maza O. Infection with HIV is associated with elevated IL-6 levels and production. J Immunol. 1990 Jan 15;144(2):480–484. [PubMed] [Google Scholar]
  6. Delecluse H. J., Raphael M., Magaud J. P., Felman P., Alsamad I. A., Bornkamm G. W., Lenoir G. M. Variable morphology of human immunodeficiency virus-associated lymphomas with c-myc rearrangements. The French Study Group of Pathology for Human Immunodeficiency Virus-Associated Tumors, I. Blood. 1993 Jul 15;82(2):552–563. [PubMed] [Google Scholar]
  7. Evan G. I., Wyllie A. H., Gilbert C. S., Littlewood T. D., Land H., Brooks M., Waters C. M., Penn L. Z., Hancock D. C. Induction of apoptosis in fibroblasts by c-myc protein. Cell. 1992 Apr 3;69(1):119–128. doi: 10.1016/0092-8674(92)90123-t. [DOI] [PubMed] [Google Scholar]
  8. Goedert J. J., Biggar R. J., Melbye M., Mann D. L., Wilson S., Gail M. H., Grossman R. J., DiGioia R. A., Sanchez W. C., Weiss S. H. Effect of T4 count and cofactors on the incidence of AIDS in homosexual men infected with human immunodeficiency virus. JAMA. 1987 Jan 16;257(3):331–334. [PubMed] [Google Scholar]
  9. Ioachim H. L., Dorsett B., Cronin W., Maya M., Wahl S. Acquired immunodeficiency syndrome-associated lymphomas: clinical, pathologic, immunologic, and viral characteristics of 111 cases. Hum Pathol. 1991 Jul;22(7):659–673. doi: 10.1016/0046-8177(91)90288-z. [DOI] [PubMed] [Google Scholar]
  10. Karp J. E., Broder S. The pathogenesis of AIDS lymphomas: a foundation for addressing the challenges of therapy and prevention. Leuk Lymphoma. 1992 Oct;8(3):167–188. doi: 10.3109/10428199209054903. [DOI] [PubMed] [Google Scholar]
  11. Liu J., Li H., de Tribolet N., Jaufeerally R., Hamou M. F., Van Meir E. G. IL-6 stimulates growth and inhibits constitutive, protein synthesis-independent apoptosis of murine B-cell hybridoma 7TD1. Cell Immunol. 1994 May;155(2):428–435. doi: 10.1006/cimm.1994.1135. [DOI] [PubMed] [Google Scholar]
  12. Milner A. E., Grand R. J., Waters C. M., Gregory C. D. Apoptosis in Burkitt lymphoma cells is driven by c-myc. Oncogene. 1993 Dec;8(12):3385–3391. [PubMed] [Google Scholar]
  13. Neurath M. F., Strober W., Wakatsuki Y. The murine Ig 3' alpha enhancer is a target site with repressor function for the B cell lineage-specific transcription factor BSAP (NF-HB, S alpha-BP). J Immunol. 1994 Jul 15;153(2):730–742. [PubMed] [Google Scholar]
  14. Rabbitts T. H., Forster A., Hamlyn P., Baer R. Effect of somatic mutation within translocated c-myc genes in Burkitt's lymphoma. Nature. 1984 Jun 14;309(5969):592–597. doi: 10.1038/309592a0. [DOI] [PubMed] [Google Scholar]
  15. Rabkin C. S., Yellin F. Cancer incidence in a population with a high prevalence of infection with human immunodeficiency virus type 1. J Natl Cancer Inst. 1994 Nov 16;86(22):1711–1716. doi: 10.1093/jnci/86.22.1711. [DOI] [PubMed] [Google Scholar]
  16. Yonish-Rouach E., Resnitzky D., Lotem J., Sachs L., Kimchi A., Oren M. Wild-type p53 induces apoptosis of myeloid leukaemic cells that is inhibited by interleukin-6. Nature. 1991 Jul 25;352(6333):345–347. doi: 10.1038/352345a0. [DOI] [PubMed] [Google Scholar]
  17. Zajac-Kaye M., Gelmann E. P., Levens D. A point mutation in the c-myc locus of a Burkitt lymphoma abolishes binding of a nuclear protein. Science. 1988 Jun 24;240(4860):1776–1780. doi: 10.1126/science.2454510. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES