Skip to main content
NCBI home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1987 Mar 1;165(3):879–890. doi: 10.1084/jem.165.3.879

Rearrangements of immunoglobulin and T cell receptor beta and gamma genes are associated with terminal deoxynucleotidyl transferase expression in acute myeloid leukemia

PMCID: PMC2188294  PMID: 3102679

Abstract

The cell origin of the rare terminal deoxynucleotidyl transferase (TdT)- positive acute myeloid leukemias (AML) was investigated at the molecular level, by examining the configuration of the Ig H (Igh) and L (Ig kappa, Ig lambda) chain gene regions, and of the T cell receptor (TCR) beta and T cell rearranging (TRG) gamma loci. In 8 of the 10 TdT+ AML analyzed (classified as myeloid according to morphological and cytochemical criteria, and to the reactivity with one or more antimyeloid mAbs), a rearrangement of the Igh chain gene was found. In TdT- AML, evidence of an Igh gene reorganization was instead observed only in 2 of the 42 patients studied. Furthermore, evidence of TCR-beta and/or TRG-gamma gene rearrangement was observed in four AML, all of which belonged to the Igh-rearranged TdT+ group. In three cases (one TdT+ and two TdT-), the Ig kappa L chain gene was also in a rearranged position. These findings demonstrate a highly significant correlation between TdT expression and DNA rearrangements at the Igh and TCR chain gene regions and support the view that this enzyme plays an important role in the V-(D)-J recombination machinery. Overall, the genomic configuration, i.e., JH gene rearrangement sometimes coupled to a kappa L chain and TCR gene reorganization, similar to that found in non-T- ALL, suggests that in most cases of TdT+ AML, the neoplastic clone, despite the expression of myeloid-related features, is characterized by cells molecularly committed along the B cell lineage.

Full Text

The Full Text of this article is available as a PDF (922.8 KB).

Selected References

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

  1. Aisenberg A. C., Krontiris T. G., Mak T. W., Wilkes B. M. Rearrangement of the gene for the beta chain of the T-cell receptor in T-cell chronic lymphocytic leukemia and related disorders. N Engl J Med. 1985 Aug 29;313(9):529–533. doi: 10.1056/NEJM198508293130901. [DOI] [PubMed] [Google Scholar]
  2. Alt F. W., Baltimore D. Joining of immunoglobulin heavy chain gene segments: implications from a chromosome with evidence of three D-JH fusions. Proc Natl Acad Sci U S A. 1982 Jul;79(13):4118–4122. doi: 10.1073/pnas.79.13.4118. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Askew D. S., Eaves A. C., Takei F. NHL-30.5: a monoclonal antibody reactive with an acute myeloid leukemia (AML)-associated antigen. Leuk Res. 1985;9(1):135–145. doi: 10.1016/0145-2126(85)90027-x. [DOI] [PubMed] [Google Scholar]
  4. Bollum F. J. Terminal deoxynucleotidyl transferase: biological studies. Adv Enzymol Relat Areas Mol Biol. 1978;47:347–374. doi: 10.1002/9780470122921.ch6. [DOI] [PubMed] [Google Scholar]
  5. Cheng G. Y., Minden M. D., Toyonaga B., Mak T. W., McCulloch E. A. T cell receptor and immunoglobulin gene rearrangements in acute myeloblastic leukemia. J Exp Med. 1986 Feb 1;163(2):414–424. doi: 10.1084/jem.163.2.414. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Desiderio S. V., Yancopoulos G. D., Paskind M., Thomas E., Boss M. A., Landau N., Alt F. W., Baltimore D. Insertion of N regions into heavy-chain genes is correlated with expression of terminal deoxytransferase in B cells. Nature. 1984 Oct 25;311(5988):752–755. doi: 10.1038/311752a0. [DOI] [PubMed] [Google Scholar]
  7. Foa R., Migone N., Basso G., Cattoretti G., Pizzolo G., Lauria F., Casorati G., Giubellino M. C., Capuzzo F., Cantù-Rajnoldi A. Molecular and immunological evidence of B-cell commitment in "null" acute lymphoblastic leukaemia. Int J Cancer. 1986 Sep 15;38(3):317–323. doi: 10.1002/ijc.2910380304. [DOI] [PubMed] [Google Scholar]
  8. Foa R., Migone N., Gavosto F. Immunological and molecular classification of acute lymphoblastic leukemia. Haematologica. 1986 Jul-Aug;71(4):277–285. [PubMed] [Google Scholar]
  9. 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]
  10. Foa R., Pelicci P. G., Migone N., Lauria F., Pizzolo G., Flug F., Knowles D. M., 2nd, Dalla-Favera R. Analysis of T-cell receptor beta chain (T beta) gene rearrangements demonstrates the monoclonal nature of T-cell chronic lymphoproliferative disorders. Blood. 1986 Jan;67(1):247–250. [PubMed] [Google Scholar]
  11. Foà R., Baldini L., Cattoretti G., Foa P., Gobbi M., Lauria F., Madon E., Masera G., Miniero R., Paolucci P. Multimarker phenotypic characterization of adult and childhood acute lymphoblastic leukaemia: an Italian multicentre study. Br J Haematol. 1985 Oct;61(2):251–259. doi: 10.1111/j.1365-2141.1985.tb02823.x. [DOI] [PubMed] [Google Scholar]
  12. Greaves M. F., Chan L. C., Furley A. J., Watt S. M., Molgaard H. V. Lineage promiscuity in hemopoietic differentiation and leukemia. Blood. 1986 Jan;67(1):1–11. [PubMed] [Google Scholar]
  13. Ha K., Minden M., Hozumi N., Gelfand E. W. Immunoglobulin gene rearrangement in acute myelogenous leukemia. Cancer Res. 1984 Oct;44(10):4658–4660. [PubMed] [Google Scholar]
  14. 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]
  15. 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]
  16. Jani P., Verbi W., Greaves M. F., Bevan D., Bollum F. Terminal deoxynucleotidyl transferase in acute myeloid leukaemia. Leuk Res. 1983;7(1):17–29. doi: 10.1016/0145-2126(83)90054-1. [DOI] [PubMed] [Google Scholar]
  17. 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]
  18. 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]
  19. Lefranc M. P., Forster A., Rabbitts T. H. Rearrangement of two distinct T-cell gamma-chain variable-region genes in human DNA. 1986 Jan 30-Feb 5Nature. 319(6052):420–422. doi: 10.1038/319420a0. [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. Migone N., Feder J., Cann H., van West B., Hwang J., Takahashi N., Honjo T., Piazza A., Cavalli-Sforza L. L. Multiple DNA fragment polymorphisms associated with immunoglobulin mu chain switch-like regions in man. Proc Natl Acad Sci U S A. 1983 Jan;80(2):467–471. doi: 10.1073/pnas.80.2.467. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. 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]
  23. Pelicci P. G., Knowles D. M., 2nd, Dalla Favera R. Lymphoid tumors displaying rearrangements of both immunoglobulin and T cell receptor genes. J Exp Med. 1985 Sep 1;162(3):1015–1024. doi: 10.1084/jem.162.3.1015. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. 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]
  25. Rambaldi A., Pelicci P. G., Allavena P., Knowles D. M., 2nd, Rossini S., Bassan R., Barbui T., Dalla-Favera R., Mantovani A. T cell receptor beta chain gene rearrangements in lymphoproliferative disorders of large granular lymphocytes/natural killer cells. J Exp Med. 1985 Dec 1;162(6):2156–2162. doi: 10.1084/jem.162.6.2156. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Rovigatti U., Mirro J., Kitchingman G., Dahl G., Ochs J., Murphy S., Stass S. Heavy chain immunoglobulin gene rearrangement in acute nonlymphocytic leukemia. Blood. 1984 May;63(5):1023–1027. [PubMed] [Google Scholar]
  27. Smith L. J., Curtis J. E., Messner H. A., Senn J. S., Furthmayr H., McCulloch E. A. Lineage infidelity in acute leukemia. Blood. 1983 Jun;61(6):1138–1145. [PubMed] [Google Scholar]
  28. Todd R. F., 3rd, Roach J. A., Arnaout M. A. The modulated expression of Mo5, a human myelomonocytic plasma membrane antigen. Blood. 1985 Apr;65(4):964–973. [PubMed] [Google Scholar]
  29. Waldmann T. A., Davis M. M., Bongiovanni K. F., Korsmeyer S. J. Rearrangements of genes for the antigen receptor on T cells as markers of lineage and clonality in human lymphoid neoplasms. N Engl J Med. 1985 Sep 26;313(13):776–783. doi: 10.1056/NEJM198509263131303. [DOI] [PubMed] [Google Scholar]
  30. Yancopoulos G. D., Blackwell T. K., Suh H., Hood L., Alt F. W. Introduced T cell receptor variable region gene segments recombine in pre-B cells: evidence that B and T cells use a common recombinase. Cell. 1986 Jan 31;44(2):251–259. doi: 10.1016/0092-8674(86)90759-2. [DOI] [PubMed] [Google Scholar]
  31. Yoshikai Y., Anatoniou D., Clark S. P., Yanagi Y., Sangster R., Van den Elsen P., Terhorst C., Mak T. W. Sequence and expression of transcripts of the human T-cell receptor beta-chain genes. Nature. 1984 Dec 6;312(5994):521–524. doi: 10.1038/312521a0. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES