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. 1989 Apr;83(4):1277–1283. doi: 10.1172/JCI114012

Rearrangement of variable region T cell receptor gamma genes in acute lymphoblastic leukemia. V gamma gene usage differs in mature and immature T cells.

J Hara 1, S H Benedict 1, K Yumura 1, K Ha-Kawa 1, E W Gelfand 1
PMCID: PMC303818  PMID: 2522937

Abstract

Using probes recognizing variable regions (V gamma) and joining regions (J gamma) of the T cell receptor (TCR) gamma gene, we have analyzed the usage of V gamma genes in 24 patients with T cell acute lymphoblastic leukemia (ALL) and 36 patients with B-precursor ALL. In CD3- T-ALL derived from immature T cells, V gamma genes more proximal to J gamma were frequently rearranged; V gamma 8, V gamma 9, V gamma 10, and V gamma 11 were used in 19 of 24 rearrangements. In contrast, CD3+ T-ALL derived from a more mature stage of T cell ontogeny, showed a high frequency of rearrangements involving V gamma genes distal to J gamma; V gamma 2, V gamma 3, V gamma 4, and V gamma 5 were used in 17 of 25 rearrangements. In B-precursor ALL, no notable bias of V gamma gene usage was observed. This probably reflects the possibility that TCR genes may not rearrange according to a T cell hierarchy when under control of a B cell gene program. Furthermore, deletions of those V gamma genes located 3' to rearranged V gamma genes were observed in all patients analyzed. This supports the theory that loop deletion is a major mechanism for TCR-gamma gene rearrangement.

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Selected References

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

  1. Bank I., DePinho R. A., Brenner M. B., Cassimeris J., Alt F. W., Chess L. A functional T3 molecule associated with a novel heterodimer on the surface of immature human thymocytes. Nature. 1986 Jul 10;322(6075):179–181. doi: 10.1038/322179a0. [DOI] [PubMed] [Google Scholar]
  2. Boehm T. L., Werle A., Ganser A., Kornhuber B., Drahovsky D. T cell receptor gamma chain variable gene rearrangements in acute lymphoblastic leukemias of T and B lineage. Eur J Immunol. 1987 Nov;17(11):1593–1597. doi: 10.1002/eji.1830171111. [DOI] [PubMed] [Google Scholar]
  3. Borst J., van de Griend R. J., van Oostveen J. W., Ang S. L., Melief C. J., Seidman J. G., Bolhuis R. L. A T-cell receptor gamma/CD3 complex found on cloned functional lymphocytes. Nature. 1987 Feb 19;325(6106):683–688. doi: 10.1038/325683a0. [DOI] [PubMed] [Google Scholar]
  4. Brenner M. B., McLean J., Dialynas D. P., Strominger J. L., Smith J. A., Owen F. L., Seidman J. G., Ip S., Rosen F., Krangel M. S. Identification of a putative second T-cell receptor. Nature. 1986 Jul 10;322(6075):145–149. doi: 10.1038/322145a0. [DOI] [PubMed] [Google Scholar]
  5. Brenner M. B., McLean J., Scheft H., Riberdy J., Ang S. L., Seidman J. G., Devlin P., Krangel M. S. Two forms of the T-cell receptor gamma protein found on peripheral blood cytotoxic T lymphocytes. Nature. 1987 Feb 19;325(6106):689–694. doi: 10.1038/325689a0. [DOI] [PubMed] [Google Scholar]
  6. Chen Z., Le Paslier D., Dausset J., Degos L., Flandrin G., Cohen D., Sigaux F. Human T cell gamma genes are frequently rearranged in B-lineage acute lymphoblastic leukemias but not in chronic B cell proliferations. J Exp Med. 1987 Apr 1;165(4):1000–1015. doi: 10.1084/jem.165.4.1000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. 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]
  8. Forster A., Huck S., Ghanem N., Lefranc M. P., Rabbitts T. H. New subgroups in the human T cell rearranging V gamma gene locus. EMBO J. 1987 Jul;6(7):1945–1950. doi: 10.1002/j.1460-2075.1987.tb02456.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Fujimoto S., Yamagishi H. Isolation of an excision product of T-cell receptor alpha-chain gene rearrangements. Nature. 1987 May 21;327(6119):242–243. doi: 10.1038/327242a0. [DOI] [PubMed] [Google Scholar]
  10. Greaves M. F., Janossy G., Peto J., Kay H. Immunologically defined subclasses of acute lymphoblastic leukaemia in children: their relationship to presentation features and prognosis. Br J Haematol. 1981 Jun;48(2):179–197. [PubMed] [Google Scholar]
  11. Greaves M., Janossy G. Patterns of gene expression and the cellular origins of human leukaemias. Biochim Biophys Acta. 1978 Oct 27;516(2):193–230. doi: 10.1016/0304-419x(78)90008-2. [DOI] [PubMed] [Google Scholar]
  12. Ha K., Hozumi N., Hrincu A., Gelfand E. W. Lineage specific classification of leukaemia: results of the analysis of sixty cases of childhood leukaemia. Br J Haematol. 1985 Oct;61(2):237–249. doi: 10.1111/j.1365-2141.1985.tb02822.x. [DOI] [PubMed] [Google Scholar]
  13. Hara J., Benedict S. H., Champagne E., Mak T. W., Minden M., Gelfand E. W. Comparison of T cell receptor alpha, beta, and gamma gene rearrangement and expression in T cell acute lymphoblastic leukemia. J Clin Invest. 1988 Apr;81(4):989–996. doi: 10.1172/JCI113453. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hara J., Benedict S. H., Mak T. W., Gelfand E. W. T cell receptor alpha-chain gene rearrangements in B-precursor leukemia are in contrast to the findings in T cell acute lymphoblastic leukemia. Comparative study of T cell receptor gene rearrangement in childhood leukemia. J Clin Invest. 1987 Dec;80(6):1770–1777. doi: 10.1172/JCI113270. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hara J., Kawa-Ha K., Yumura K., Ishihara S., Doi S., Yabuuchi H., Konishi S., Nishikawa A. Heterogeneity of acute undifferentiated leukemia at the immunoglobulin and T-cell receptor genes level. Jpn J Cancer Res. 1987 Feb;78(2):170–175. [PubMed] [Google Scholar]
  16. Huck S., Dariavach P., Lefranc M. P. Variable region genes in the human T-cell rearranging gamma (TRG) locus: V-J junction and homology with the mouse genes. EMBO J. 1988 Mar;7(3):719–726. doi: 10.1002/j.1460-2075.1988.tb02868.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kleinfield R., Hardy R. R., Tarlinton D., Dangl J., Herzenberg L. A., Weigert M. Recombination between an expressed immunoglobulin heavy-chain gene and a germline variable gene segment in a Ly 1+ B-cell lymphoma. 1986 Aug 28-Sep 3Nature. 322(6082):843–846. doi: 10.1038/322843a0. [DOI] [PubMed] [Google Scholar]
  18. 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]
  19. LeFranc M. P., Forster A., Baer R., Stinson M. A., Rabbitts T. H. Diversity and rearrangement of the human T cell rearranging gamma genes: nine germ-line variable genes belonging to two subgroups. Cell. 1986 Apr 25;45(2):237–246. doi: 10.1016/0092-8674(86)90388-0. [DOI] [PubMed] [Google Scholar]
  20. Lefranc M. P., Rabbitts T. H. Two tandemly organized human genes encoding the T-cell gamma constant-region sequences show multiple rearrangement in different T-cell types. Nature. 1985 Aug 1;316(6027):464–466. doi: 10.1038/316464a0. [DOI] [PubMed] [Google Scholar]
  21. Nadler L. M., Korsmeyer S. J., Anderson K. C., Boyd A. W., Slaughenhoupt B., Park E., Jensen J., Coral F., Mayer R. J., Sallan S. E. B cell origin of non-T cell acute lymphoblastic leukemia. A model for discrete stages of neoplastic and normal pre-B cell differentiation. J Clin Invest. 1984 Aug;74(2):332–340. doi: 10.1172/JCI111428. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Okazaki K., Davis D. D., Sakano H. T cell receptor beta gene sequences in the circular DNA of thymocyte nuclei: direct evidence for intramolecular DNA deletion in V-D-J joining. Cell. 1987 May 22;49(4):477–485. doi: 10.1016/0092-8674(87)90450-8. [DOI] [PubMed] [Google Scholar]
  23. Quertermous T., Murre C., Dialynas D., Duby A. D., Strominger J. L., Waldman T. A., Seidman J. G. Human T-cell gamma chain genes: organization, diversity, and rearrangement. Science. 1986 Jan 17;231(4735):252–255. doi: 10.1126/science.3079918. [DOI] [PubMed] [Google Scholar]
  24. Quertermous T., Strauss W. M., Van Dongen J. J., Seidman J. G. Human T cell gamma chain joining regions and T cell development. J Immunol. 1987 Apr 15;138(8):2687–2690. [PubMed] [Google Scholar]
  25. Reth M., Gehrmann P., Petrac E., Wiese P. A novel VH to VHDJH joining mechanism in heavy-chain-negative (null) pre-B cells results in heavy-chain production. 1986 Aug 28-Sep 3Nature. 322(6082):840–842. doi: 10.1038/322840a0. [DOI] [PubMed] [Google Scholar]
  26. Saito H., Kranz D. M., Takagaki Y., Hayday A. C., Eisen H. N., Tonegawa S. A third rearranged and expressed gene in a clone of cytotoxic T lymphocytes. Nature. 1984 Nov 1;312(5989):36–40. doi: 10.1038/312036a0. [DOI] [PubMed] [Google Scholar]
  27. Strauss W. M., Quertermous T., Seidman J. G. Measuring the human T cell receptor gamma-chain locus. Science. 1987 Sep 4;237(4819):1217–1219. doi: 10.1126/science.3498213. [DOI] [PubMed] [Google Scholar]
  28. Sugiyama H., Maeda T., Tani Y., Miyake S., Oka Y., Komori T., Ogawa H., Soma T., Minami Y., Sakato N. Selective use of the VHQ52 family in functional VH to DJH rearrangements in a B precursor cell line. J Exp Med. 1987 Aug 1;166(2):607–612. doi: 10.1084/jem.166.2.607. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Tawa A., Benedict S. H., Hara J., Hozumi N., Gelfand E. W. Rearrangement of the T cell receptor gamma-chain gene in childhood acute lymphoblastic leukemia. Blood. 1987 Dec;70(6):1933–1939. [PubMed] [Google Scholar]
  30. Tawa A., Hozumi N., Minden M., Mak T. W., Gelfand E. W. Rearrangement of the T-cell receptor beta-chain gene in non-T-cell, non-B-cell acute lymphoblastic leukemia of childhood. N Engl J Med. 1985 Oct 24;313(17):1033–1037. doi: 10.1056/NEJM198510243131701. [DOI] [PubMed] [Google Scholar]
  31. Yancopoulos G. D., Alt F. W. Regulation of the assembly and expression of variable-region genes. Annu Rev Immunol. 1986;4:339–368. doi: 10.1146/annurev.iy.04.040186.002011. [DOI] [PubMed] [Google Scholar]
  32. Yoshikai Y., Toyonaga B., Koga Y., Kimura N., Griesser H., Mak T. W. Repertoire of the human T cell gamma genes: high frequency of nonfunctional transcripts in thymus and mature T cells. Eur J Immunol. 1987 Jan;17(1):119–126. doi: 10.1002/eji.1830170120. [DOI] [PubMed] [Google Scholar]

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