Abstract
A case of non‐Hodgkin's lymphoma showed a phenotypic and genotypic cell lineage switch twice during nine years of his clinical history; first, T‐cell type, pleomorphic small cell lymphoma developed, followed by B‐cell type, diffuse centroblastic/centrocytic lymphoma, and finally T‐zone lymphoma without follicles again developed, from which AST‐1 cultured cell line was established. Karyotype analysis demonstrated a shared abnormal chromosome, der(1)t(1;?)(p36;?), among the first relapsed B‐cell tumor, the second relapsed T‐cell tumor and AST‐1 cell line. Furthermore, T‐cell receptor (TCR) γ gene rearrangement bands of the same size were observed in the first relapsed B‐cell tumor and the second relapsed T‐cell tumor as well as AST‐1 cell line. These results suggested that both relapsed tumors of different cell lineages are derived from a common malignant clone, presumably a committed lymphoid stem cell. A unique translocation, t(2;14)(q37;q11.2), which may involve TCR δ/α gene complex, was observed in the second relapsed tumor and AST‐1 cells. To attempt to isolate the breakpoint of this translocation, the configuration of TCR δ/α gene complex was studied. The result showed that two rearrangements of TCR α gene detected with Jα probes were the products of the normal TCR rearrangement process, and were not involved in the translocation at this region. This patient, together with the AST‐1 cell line, provided us a unique opportunity to study the development and clonal evolution of malignant lymphoma.
Keywords: Key words, Lymphoma, Chromosome translocation, Stem cell, T‐cell, B‐cell
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REFERENCES
- 1. ) Stein , H. , Lennert , K. , Feller , A. and Mason , D. Y.Immunohistological analysis of human lymphoma: correlation of histological and immunological categories . Adv. Cancer Res. , 42 , 67 – 147 ( 1984. ). [DOI] [PubMed] [Google Scholar]
- 2. ) Korsmeyer , S. J.Antigen receptor genes as molecular markers of lymphoid neoplasms . J. Clin. Invest. , 79 , 1291 – 1295 ( 1987. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3. ) Griesser , H. , Tkachuk , D. , Reis , M. D. and Mak , T. W.Gene rearrangements and translocations in lymphoproliferative diseases . Blood , 73 , 1402 – 1415 ( 1989. ). [PubMed] [Google Scholar]
- 4. ) Rowley , J. D.Molecular cytogenetics: Rosetta stone for understanding cancer . Cancer Res. , 50 , 3816 – 3825 ( 1990. ). [PubMed] [Google Scholar]
- 5. ) Heim , S. and Mitelman , F.Primary chromosome abnormalities in human neoplasia . Adv. Cancer Res. , 52 , 1 – 43 ( 1989. ). [DOI] [PubMed] [Google Scholar]
- 6. ) York , J. C. , Cousar , J. B. , Glick , A. D. , Flexner , J. M. , Stein , R. and Collins , R. D.Morphologic and immunologic evidence of composite B‐ and T‐cell lymphomas. A report of three cases developing in follicular center cell lymphomas . Am. J. Clin. Pathol. , 84 , 35 – 43 ( 1985. ). [DOI] [PubMed] [Google Scholar]
- 7. ) Sklar , J. , Cleary , M. L. , Thielemans , K. , Gralow , J. , Warnke , R. and Levy , R.Biclonal B‐cell lymphoma . N. Engl. J. Med. , 311 , 20 – 27 ( 1984. ). [DOI] [PubMed] [Google Scholar]
- 8. ) Cleary , M. L. , Galili , N. , Trela , M. , Levy , R. and Sklar , J.Single cell origin of bigenotypic and biphenotypic B cell proliferations in human follicular lymphomas . J. Exp. Switch Med. , 167 , 582 – 597 ( 1988. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9. ) Miyamura , K. , Osada , H. , Yamauchi , T. , Itoh , M. , Kodera , Y. , Suchi , T. , Takahashi , T. and Ueda , R.Single clonal origin of neoplastic B‐cells with different immunoglobulin light chains in a patient with Richter's syndrome . Cancer , 66 , 140 – 144 ( 1990. ). [DOI] [PubMed] [Google Scholar]
- 10. ) Jennette , J. C. , Reddick , R. L. , Saunders , A. W. and Wilkman , A. S.Diffuse T‐cell lymphoma preceded by nodular lymphoma . Am, J. Clin. Pathol. , 78 , 242 – 248 ( 1982. ). [DOI] [PubMed] [Google Scholar]
- 11. ) Hu , E. , Weiss , L. M. , Warnke , R. and Sklar , J.Non‐Hodgkin's lymphoma containing both B and T cell clones . Blood , 70 , 287 – 292 ( 1987. ). [PubMed] [Google Scholar]
- 12. ) Shimizu , K. , Hirano , M. , Maruyama , F. , Itoh , M. , Hara , K. , Ino , T. , Ezaki , K. and Kunii , A.T‐cell malignancy following B‐cell lymphoma in remission . Am. J. Clin. Pathol. , 92 , 362 – 366 ( 1989. ). [DOI] [PubMed] [Google Scholar]
- 13. ) Cotter , F. E. , Hall , P. A. , Young , B. D. and Lister , T. A.Simultaneous presentation of T‐ and B‐cell malignant lymphoma with bcl‐2 gene involvement . Blood , 73 , 1387 – 1388 ( 1989. ). [PubMed] [Google Scholar]
- 14. ) Stansfeld , A. G. , Diebold , J. , Noel , H. , Kapanci , Y. , Rilke , F. , Kelenyi , G. , Sundstrom , C. , Lennert , K. , van Unnik , J. A. M. , Mioduszewska , O. and Wright , D. H.Updated Kiel classification for lymphomas . Lancet , i , 292 – 293 ( 1988. ). [DOI] [PubMed] [Google Scholar]
- 15. ) Hsu , S‐M. , Raine , L. and Fanger , H.Use of avidin‐biotin peroxidase complexes (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures . J. Histochem. Cytochem. , 25 , 577 – 580 ( 1981. ). [DOI] [PubMed] [Google Scholar]
- 16. ) Ogura , M. , Morishima , Y. , Ohno , R. , Kato , Y. , Hirabayashi , N. , Nagura , H. and Saito , H.Establishment of a novel human megakaryoblastic leukemia cell line, MEG‐01, with positive Philadelphia chromosome . Blood , 66 , 1384 – 1392 ( 1985. ). [PubMed] [Google Scholar]
- 17. ) Morishima , Y. , Ohya , K. , Ueda , R. and Fukuda , T.Detection of adult T‐cell leukemia virus (ATLV) bearing lymphocytes in concentrated red blood cell derived from ATL associated antibody (ATLA‐Ab) positive donors . Vox. Sang. , 50 , 212 – 215 ( 1986. ). [DOI] [PubMed] [Google Scholar]
- 18. ) Reedman , B. M. , Klein , G. , Pope , J. H. , Walter , M. K. , Hilgers , J. , Singh , S. and Johansson , B.Epstein‐Barr virus‐associated complement fixing and nuclear antigens in Burkitt lymphoma biopsies . Int. J. Cancer , 13 , 755 – 763 ( 1974. ). [DOI] [PubMed] [Google Scholar]
- 19. ) Seabright , M. Arapid banding technique for human chromosomes . Lancet , ii , 971 – 972 ( 1971. ). [DOI] [PubMed] [Google Scholar]
- 20. ) Suzuki , H. , Ueda , R. , Obata , Y. , Seto , M. , Hirata , R. , Iwamura , H. , Ota , K. and Takahashi , T. Tcell receptor β chain gene rearrangements in leukemias with immature T cell phenotype . Jpn. J. Cancer Res. , 11 , 1069 – 1073 ( 1986. ). [PubMed] [Google Scholar]
- 21. ) Suzuki , H. , Namikawa , R. , Ueda , R. , Obata , Y. , Suchi , T. , Kikuchi , M. , Ota , K. and Takahashi , T.Clonal T cell population in angioimmunoblastic lymphadenopathy and related lesions . Jpn. J. Cancer Res. , 78 , 712 – 720 ( 1987. ). [PubMed] [Google Scholar]
- 22. ) Korsmeyer , S. J. , Arnold , A. , Bakhshi , A. , Ravetch , J. V. , Siebenlist , U. , Hieter , P. H. , Sharrow , S. O. , LeBien , T. W. , Kersey , J. H. , Poplack , D. G. , Leder , P. and Waldmann , T. A.Immunoglobulin gene rearrangements and cell surface antigen expression in acute lymphocytic leukemias of T cell and B cell precursor origins . J. Clin. Invest. , 71 , 301 – 313 ( 1983. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23. ) Yoshikai , Y. , Anatoniou , D. , Clark , S. P. , Yanagi , Y. , Sangster , R. , Van den Elsen , P. , Terhorst , C. and Mak , T. W.Sequence and expression of transcripts of the human T‐cell receptor β chain genes . Nature , 312 , 521 – 524 ( 1984. ). [DOI] [PubMed] [Google Scholar]
- 24. ) Ino , T. , Kurosawa , Y. , Yoshida , M. C. and Hirano , M.DNA segment containing Cβ1, a gene for the constatnt region of the β chain of the T‐cell antigen receptor, was inserted into chromosome 6 in cells from patients with human T‐cell leukemia . Proc. Natl. Acad. Sci. USA. , 84 , 4264 – 4267 ( 1987. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25. ) Baer , R. , Boehm , T. , Yssel , H. , Spits , H. and Rabbitts , T. H.Complex rearrangements within the human Jδ‐Cδ/Jα‐Cα locus and aberrant recombination between Jα segments . EMBO J. , 7 , 1661 – 1668 ( 1988. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26. ) Isobe , M. , Russo , G. , Haluska , F. G. and Croce , C. M.Cloning of the gene encoding the δ subunit of the human T‐cell receptor reveals its physical organization within the a‐subunit locus and its involvement in chromosome translocations in T‐cell malignancy . Proc. Natl. Acad. Sci. USA , 85 , 3933 – 3937 ( 1988. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27. ) Lefranc , M. P. and Rabbitts , T. H.Two tandemly organized human genes encoding the T‐cell constant region sequences show multiple rearrangement in different T cell types . Nature , 316 , 464 – 466 ( 1985. ). [DOI] [PubMed] [Google Scholar]
- 28. ) Norton , A. J. , Ramsay , A. D. , Smith , S. H. , Beverly , P. C. L. and Isaacson , P. G.Monoclonal antibody (UCHL1) that recognizes normal and neoplastic T cells in routinely fixed tissues . J. Clin. Pathol. , 39 , 399 – 405 ( 1986. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29. ) Poppema , S. , Hollema , H. , Visser , L. and Vos , H.Monoclonal antibodies (MT1, MT2, MB1, MB2, MB3) reactive with leukocyte subsets in paraffin‐embedded tissue sections . Am. J. Pathol. , 127 , 418 – 429 ( 1987. ). [PMC free article] [PubMed] [Google Scholar]
- 30. ) Cartun , R. W. , Coles , F. B. and Pastuszak , W. T.Utilization of monoclonal antibody L26 in the identification and confirmation of B‐cell lymphomas . Am. J. Pathol. , 129 , 415 – 421 ( 1987. ). [PMC free article] [PubMed] [Google Scholar]
- 31. ) Ruben , S. , Poteat , H. , Tan , T‐H. , Kawakami , K. , Roeder , R. , Haseltine , W. and Rosen , C. A.Cellular transcription factors and regulation of IL‐2 receptor gene expression by HTLV‐1 tax gene product . Science , 241 , 89 – 92 ( 1988. ). [DOI] [PubMed] [Google Scholar]
- 32. ) Krikorian , J. G. , Burke , J. S. , Rosenberg , S. A. and Kaplan , H. S.Occurrence of non‐Hodgkin's lymphoma after therapy for Hodgkin's disease . N. Engl. J. Med. , 300 , 452 – 458 ( 1979. ). [DOI] [PubMed] [Google Scholar]
- 33. ) Zarrabi , M. H.Association of non‐Hodgkin's lymphoma (NHL) and second neoplasms . Semin. Oncol. , 1 , 340 – 351 ( 1980. ). [PubMed] [Google Scholar]
- 34. ) Porcelli , S. , Brenner , M. B. and Band , H.Biology of the human γδ T‐cell receptor . Immunol. Rev. , 120 , 137 – 183 ( 1991. ). [DOI] [PubMed] [Google Scholar]
- 35. ) Chen , Z. , Le Paslier , D. , Dausset , J. , Degos , L. , Flandrin , G. , Cohen , D. and Sigaux , F.Human T cell γ genes are frequently rearranged in B‐lineage acute lymphoblastic leukemias, but not in chronic B cell proliferations . J. Exp. Med. , 165 , 1000 – 1015 ( 1987. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 36. ) Greaves , M. F.Differentiation‐linked leukemogenesis in lymphocytes . Science , 234 , 697 – 704 ( 1986. ). [DOI] [PubMed] [Google Scholar]
- 37. ) Trent , J. M. , Kaneko , Y. and Mitelman , F.Report of the committee on structural chromosome changes in neoplasia . Cytogenet. Cell Genet. , 51 , 533 – 562 ( 1989. ). [DOI] [PubMed] [Google Scholar]
- 38. ) Yunis , J. J. , Soreng , A. L. and Bowe , A. E.Fragile sites are targets of diverse mutagens and carcinogens . Oncogene , 1 , 59 – 69 ( 1987. ). [PubMed] [Google Scholar]
- 39. ) Welborn , J. L. , Lewis , J. P. , Jenks , H. and Walling , P.Diagnostic and prognostic significance of t(1;3)(p36;q21) in the disorders of hematopoiesis . Cancer Genet. Cytogenet. , 28 , 277 – 285 ( 1987. ). [DOI] [PubMed] [Google Scholar]
- 40. ) Bernard , O. , Larsen , C‐J. , Hampe , A. , Mauchauffe , M. , Berger , R. and Mathieu‐Mahul , D.Molecular mechanisms of a t(8;14)(q24;q11) translocation juxtaposing c‐myc and TCR‐α genes in a T‐cell leukemia: involvement of a Vα internal heptamer . Oncogene , 2 , 195 – 200 ( 1988. ). [PubMed] [Google Scholar]
- 41. ) Yoshikai , Y. , Kimura , N. , Toyonaga , B. and Mak , T. W.Sequences and repertoire of human T cell receptor a chain variable region genes in mature T lymphocytes . J. Exp. Med. , 164 , 90 – 103 ( 1986. ). [DOI] [PMC free article] [PubMed] [Google Scholar]