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. 1992 Mar;89(3):1014–1020. doi: 10.1172/JCI115642

A human lymphoma cell line with multiple immunoglobulin rearrangements.

H Chang 1, H A Messner 1, X H Wang 1, C Yee 1, L Addy 1, J Meharchand 1, M D Minden 1
PMCID: PMC442951  PMID: 1311715

Abstract

The development of a cell culture system efficient in the establishment of lymphoma cell lines has made it possible to dissect basic biological and molecular aspects of lymphoma cells. We have established a lymphoma cell line from a patient with B cell lymphoma. The cell line has a complex karyotype with translocations involving bands 8q24, 14q32, and 18q21. Molecular analysis revealed that the Myc gene was rearranged; we were unable to demonstrate rearrangement of the Bcl-2 gene. Evaluation of the structure of the heavy chain Ig genes revealed that the cell line carried the same rearrangements as the cells from which the cell line was derived. The pattern of rearrangement, however, was unusual in that there were at least four rearranged bands when DNA cut with HindIII was probed with a fragment of the heavy chain joining region. To further characterize the cell line, subclones were derived. Individual subclones had the same pattern of rearrangement as the parent cell line. The results of these studies provide evidence that multiple rearranged Ig genes may be present in a single clone of cells.

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Selected References

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

  1. Adachi M., Tefferi A., Greipp P. R., Kipps T. J., Tsujimoto Y. Preferential linkage of bcl-2 to immunoglobulin light chain gene in chronic lymphocytic leukemia. J Exp Med. 1990 Feb 1;171(2):559–564. doi: 10.1084/jem.171.2.559. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Alt F., Rosenberg N., Lewis S., Thomas E., Baltimore D. Organization and reorganization of immunoglobulin genes in A-MULV-transformed cells: rearrangement of heavy but not light chain genes. Cell. 1981 Dec;27(2 Pt 1):381–390. doi: 10.1016/0092-8674(81)90421-9. [DOI] [PubMed] [Google Scholar]
  3. Andiman W., Gradoville L., Heston L., Neydorff R., Savage M. E., Kitchingman G., Shedd D., Miller G. Use of cloned probes to detect Epstein-Barr viral DNA in tissues of patients with neoplastic and lymphoproliferative diseases. J Infect Dis. 1983 Dec;148(6):967–977. doi: 10.1093/infdis/148.6.967. [DOI] [PubMed] [Google Scholar]
  4. Arnold A., Cossman J., Bakhshi A., Jaffe E. S., Waldmann T. A., Korsmeyer S. J. Immunoglobulin-gene rearrangements as unique clonal markers in human lymphoid neoplasms. N Engl J Med. 1983 Dec 29;309(26):1593–1599. doi: 10.1056/NEJM198312293092601. [DOI] [PubMed] [Google Scholar]
  5. Bakhshi A., Minowada J., Arnold A., Cossman J., Jensen J. P., Whang-Peng J., Waldmann T. A., Korsmeyer S. J. Lymphoid blast crises of chronic myelogenous leukemia represent stages in the development of B-cell precursors. N Engl J Med. 1983 Oct 6;309(14):826–831. doi: 10.1056/NEJM198310063091404. [DOI] [PubMed] [Google Scholar]
  6. Beishuizen A., Hählen K., Hagemeijer A., Verhoeven M. A., Hooijkaas H., Adriaansen H. J., Wolvers-Tettero I. L., van Wering E. R., van Dongen J. J. Multiple rearranged immunoglobulin genes in childhood acute lymphoblastic leukemia of precursor B-cell origin. Leukemia. 1991 Aug;5(8):657–667. [PubMed] [Google Scholar]
  7. Bertoli L. F., Kubagawa H., Borzillo G. V., Burrows P. D., Schreeder M. T., Carroll A. J., Cooper M. D. Bone marrow origin of a B-cell lymphoma. Blood. 1988 Jul;72(1):94–101. [PubMed] [Google Scholar]
  8. Bertoli L. F., Kubagawa H., Borzillo G. V., Mayumi M., Prchal J. T., Kearney J. F., Durant J. R., Cooper M. D. Analysis with antiidiotype antibody of a patient with chronic lymphocytic leukemia and a large cell lymphoma (Richter's syndrome). Blood. 1987 Jul;70(1):45–50. [PubMed] [Google Scholar]
  9. Bird J., Galili N., Link M., Stites D., Sklar J. Continuing rearrangement but absence of somatic hypermutation in immunoglobulin genes of human B cell precursor leukemia. J Exp Med. 1988 Jul 1;168(1):229–245. doi: 10.1084/jem.168.1.229. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Carter M., Neale G. A., Kitchingman G. R. Characterization of immunoglobulin heavy chain genes from an acute lymphocytic leukemia with four rearrangements. Leukemia. 1991 Aug;5(8):668–672. [PubMed] [Google Scholar]
  11. Cleary M. L., Chao J., Warnke R., Sklar J. Immunoglobulin gene rearrangement as a diagnostic criterion of B-cell lymphoma. Proc Natl Acad Sci U S A. 1984 Jan;81(2):593–597. doi: 10.1073/pnas.81.2.593. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. 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]
  13. Cleary M. L., Galili N., Trela M., Levy R., Sklar J. Single cell origin of bigenotypic and biphenotypic B cell proliferations in human follicular lymphomas. J Exp Med. 1988 Feb 1;167(2):582–597. doi: 10.1084/jem.167.2.582. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Cleary M. L., Sklar J. Lymphoproliferative disorders in cardiac transplant recipients are multiclonal lymphomas. Lancet. 1984 Sep 1;2(8401):489–493. doi: 10.1016/s0140-6736(84)92566-2. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. Cleary M. L., Warnke R., Sklar J. Monoclonality of lymphoproliferative lesions in cardiac-transplant recipients. Clonal analysis based on immunoglobulin-gene rearrangements. N Engl J Med. 1984 Feb 23;310(8):477–482. doi: 10.1056/NEJM198402233100801. [DOI] [PubMed] [Google Scholar]
  17. Dalla-Favera R., Gelmann E. P., Martinotti S., Franchini G., Papas T. S., Gallo R. C., Wong-Staal F. Cloning and characterization of different human sequences related to the onc gene (v-myc) of avian myelocytomatosis virus (MC29). Proc Natl Acad Sci U S A. 1982 Nov;79(21):6497–6501. doi: 10.1073/pnas.79.21.6497. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. 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]
  19. Foa R., Migone N., Saitta M., Fierro M. T., Giubellino M. C., Lusso P., Cordero di Montezemolo L., Miniero R., Lauria F. Different stages of B cell differentiation in non-T acute lymphoblastic leukemia. J Clin Invest. 1984 Nov;74(5):1756–1763. doi: 10.1172/JCI111594. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Gauwerky C. E., Haluska F. G., Tsujimoto Y., Nowell P. C., Croce C. M. Evolution of B-cell malignancy: pre-B-cell leukemia resulting from MYC activation in a B-cell neoplasm with a rearranged BCL2 gene. Proc Natl Acad Sci U S A. 1988 Nov;85(22):8548–8552. doi: 10.1073/pnas.85.22.8548. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Gauwerky C. E., Hoxie J., Nowell P. C., Croce C. M. Pre-B-cell leukemia with a t(8; 14) and a t(14; 18) translocation is preceded by follicular lymphoma. Oncogene. 1988 May;2(5):431–435. [PubMed] [Google Scholar]
  22. Hieter P. A., Hollis G. F., Korsmeyer S. J., Waldmann T. A., Leder P. Clustered arrangement of immunoglobulin lambda constant region genes in man. Nature. 1981 Dec 10;294(5841):536–540. doi: 10.1038/294536a0. [DOI] [PubMed] [Google Scholar]
  23. Hieter P. A., Maizel J. V., Jr, Leder P. Evolution of human immunoglobulin kappa J region genes. J Biol Chem. 1982 Feb 10;257(3):1516–1522. [PubMed] [Google Scholar]
  24. Kiem H. P., Nourse J., Saltman D. L., Blume K. G., Cleary M. L. Concurrent activation of c-myc and inactivation of bcl-2 by chromosomal translocation in a lymphoblastic lymphoma cell line. Oncogene. 1990 Dec;5(12):1815–1819. [PubMed] [Google Scholar]
  25. Kitchingman G. R., Mirro J., Stass S., Rovigatti U., Melvin S. L., Williams D. L., Raimondi S. C., Murphy S. B. Biologic and prognostic significance of the presence of more than two mu heavy-chain genes in childhood acute lymphoblastic leukemia of B precursor cell origin. Blood. 1986 Mar;67(3):698–703. [PubMed] [Google Scholar]
  26. Korsmeyer S. J., Arnold A., Bakhshi A., Ravetch J. V., Siebenlist U., Hieter P. A., Sharrow S. O., LeBien T. W., Kersey J. H., Poplack D. G. Immunoglobulin gene rearrangement and cell surface antigen expression in acute lymphocytic leukemias of T cell and B cell precursor origins. J Clin Invest. 1983 Feb;71(2):301–313. doi: 10.1172/JCI110770. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Korsmeyer S. J., Hieter P. A., Ravetch J. V., Poplack D. G., Waldmann T. A., Leder P. Developmental hierarchy of immunoglobulin gene rearrangements in human leukemic pre-B-cells. Proc Natl Acad Sci U S A. 1981 Nov;78(11):7096–7100. doi: 10.1073/pnas.78.11.7096. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Levy R., Levy S., Cleary M. L., Carroll W., Kon S., Bird J., Sklar J. Somatic mutation in human B-cell tumors. Immunol Rev. 1987 Apr;96:43–58. doi: 10.1111/j.1600-065x.1987.tb00508.x. [DOI] [PubMed] [Google Scholar]
  29. Matsuzaki H., Hata H., Asou N., Suzushima H., Akahoshi Y., Yoshida M., Nagakura S., Ishii T., Sanada I., Takatsuki K. Establishment and characterization of acute B-cell lymphocytic leukemia cell line showing (8;14) and (14;18) chromosome translocation. Acta Haematol. 1990;84(3):156–161. doi: 10.1159/000205054. [DOI] [PubMed] [Google Scholar]
  30. Ostrowski M., Minden M., Wang C., Bailey D. Immunophenotypic and gene probe analysis of a case of Richter's syndrome. Am J Clin Pathol. 1989 Feb;91(2):215–221. doi: 10.1093/ajcp/91.2.215. [DOI] [PubMed] [Google Scholar]
  31. Pegoraro L., Palumbo A., Erikson J., Falda M., Giovanazzo B., Emanuel B. S., Rovera G., Nowell P. C., Croce C. M. A 14;18 and an 8;14 chromosome translocation in a cell line derived from an acute B-cell leukemia. Proc Natl Acad Sci U S A. 1984 Nov;81(22):7166–7170. doi: 10.1073/pnas.81.22.7166. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. 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]
  33. Siegelman M. H., Cleary M. L., Warnke R., Sklar J. Frequent biclonality and Ig gene alterations among B cell lymphomas that show multiple histologic forms. J Exp Med. 1985 Apr 1;161(4):850–863. doi: 10.1084/jem.161.4.850. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Sklar J., Cleary M. L., Thielemans K., Gralow J., Warnke R., Levy R. Biclonal B-cell lymphoma. N Engl J Med. 1984 Jul 5;311(1):20–27. doi: 10.1056/NEJM198407053110104. [DOI] [PubMed] [Google Scholar]
  35. Tweeddale M. E., Lim B., Jamal N., Robinson J., Zalcberg J., Lockwood G., Minden M. D., Messner H. A. The presence of clonogenic cells in high-grade malignant lymphoma: a prognostic factor. Blood. 1987 May;69(5):1307–1314. [PubMed] [Google Scholar]
  36. Vogelstein B., Fearon E. R., Hamilton S. R., Feinberg A. P. Use of restriction fragment length polymorphisms to determine the clonal origin of human tumors. Science. 1985 Feb 8;227(4687):642–645. doi: 10.1126/science.2982210. [DOI] [PubMed] [Google Scholar]
  37. 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]
  38. Yee C., Biondi A., Wang X. H., Iscove N. N., de Sousa J., Aarden L. A., Wong G. G., Clark S. C., Messner H. A., Minden M. D. A possible autocrine role for interleukin-6 in two lymphoma cell lines. Blood. 1989 Aug 1;74(2):798–804. [PubMed] [Google Scholar]

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