Abstract
We have studied a leukemic stem-cell line, DU.528, that is able to differentiate into myeloid and lymphoid cells. The leukemic cells have a translocation between chromosomes 1 and 14, t(1;14)(p33;q11), which we have molecularly cloned and sequenced. Initial screening used joining (J)-segment probes from the T-cell receptor (TCR) alpha- and delta-chain loci. In apparent concert with the translocation, a deletion has occurred between delta-chain diversity (D)-region genes D delta 1 and D delta 2. D delta 2 was observed on derivative chromosome 1 [der(1)] and D delta 1 on der(14) with a deletion of the intervening 10 kilobases of germ-line DNA. The nature of the D delta 1-D delta 2 deletional event implicates a lymphoid recombinase in the mechanism of the translocation. As a consequence of the translocation, an unusual fusion transcript was generated. Probes from chromosome 1 detected a previously unreported transcript in RNA from both the cell line and the patient. A chromosome 14 probe identified the same transcript, thus confirming a fusion transcript derived from both chromosomes 1 and 14. This translocation may identify a gene for which we propose the name SCL (stem-cell leukemia) that is important for hemopoietic development and oncogenesis and that has been disrupted or altered in this stem-cell line.
Full text
PDF




Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bakhshi A., Jensen J. P., Goldman P., Wright J. J., McBride O. W., Epstein A. L., Korsmeyer S. J. Cloning the chromosomal breakpoint of t(14;18) human lymphomas: clustering around JH on chromosome 14 and near a transcriptional unit on 18. Cell. 1985 Jul;41(3):899–906. doi: 10.1016/s0092-8674(85)80070-2. [DOI] [PubMed] [Google Scholar]
- Begley C. G., Metcalf D., Nicola N. A. Primary human myeloid leukemia cells: comparative responsiveness to proliferative stimulation by GM-CSF or G-CSF and membrane expression of CSF receptors. Leukemia. 1987 Jan;1(1):1–8. [PubMed] [Google Scholar]
- Begley C. G., Metcalf D., Nicola N. A. Purified colony stimulating factors (G-CSF and GM-CSF) induce differentiation in human HL60 leukemic cells with suppression of clonogenicity. Int J Cancer. 1987 Jan 15;39(1):99–105. doi: 10.1002/ijc.2910390118. [DOI] [PubMed] [Google Scholar]
- Caccia N., Bruns G. A., Kirsch I. R., Hollis G. F., Bertness V., Mak T. W. T cell receptor alpha chain genes are located on chromosome 14 at 14q11-14q12 in humans. J Exp Med. 1985 May 1;161(5):1255–1260. doi: 10.1084/jem.161.5.1255. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chien Y. H., Iwashima M., Wettstein D. A., Kaplan K. B., Elliott J. F., Born W., Davis M. M. T-cell receptor delta gene rearrangements in early thymocytes. Nature. 1987 Dec 24;330(6150):722–727. doi: 10.1038/330722a0. [DOI] [PubMed] [Google Scholar]
- Dalla-Favera R., Bregni M., Erikson J., Patterson D., Gallo R. C., Croce C. M. Human c-myc onc gene is located on the region of chromosome 8 that is translocated in Burkitt lymphoma cells. Proc Natl Acad Sci U S A. 1982 Dec;79(24):7824–7827. doi: 10.1073/pnas.79.24.7824. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Denny C. T., Hollis G. F., Hecht F., Morgan R., Link M. P., Smith S. D., Kirsch I. R. Common mechanism of chromosome inversion in B- and T-cell tumors: relevance to lymphoid development. Science. 1986 Oct 10;234(4773):197–200. doi: 10.1126/science.3092355. [DOI] [PubMed] [Google Scholar]
- Denny C. T., Hollis G. F., Magrath I. T., Kirsch I. R. Burkitt lymphoma cell line carrying a variant translocation creates new DNA at the breakpoint and violates the hierarchy of immunoglobulin gene rearrangement. Mol Cell Biol. 1985 Nov;5(11):3199–3207. doi: 10.1128/mcb.5.11.3199. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Denny C. T., Yoshikai Y., Mak T. W., Smith S. D., Hollis G. F., Kirsch I. R. A chromosome 14 inversion in a T-cell lymphoma is caused by site-specific recombination between immunoglobulin and T-cell receptor loci. Nature. 1986 Apr 10;320(6062):549–551. doi: 10.1038/320549a0. [DOI] [PubMed] [Google Scholar]
- Fialkow P. J., Denman A. M., Jacobson R. J., Lowenthal M. N. Chronic myelocytic leukemia. Origin of some lymphocytes from leukemic stem cells. J Clin Invest. 1978 Oct;62(4):815–823. doi: 10.1172/JCI109193. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fialkow P. J., Jacobson R. J., Papayannopoulou T. Chronic myelocytic leukemia: clonal origin in a stem cell common to the granulocyte, erythrocyte, platelet and monocyte/macrophage. Am J Med. 1977 Jul;63(1):125–130. doi: 10.1016/0002-9343(77)90124-3. [DOI] [PubMed] [Google Scholar]
- Hagemeijer A., van Dongen J. J., Slater R. M., van't Veer M. B., Behrendt H., Hählen K., Sizoo W., Abels J. Characterization of the blast cells in acute leukemia with translocation (4;11): report of eight additional cases and of one case with a variant translocation. Leukemia. 1987 Jan;1(1):24–31. [PubMed] [Google Scholar]
- 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]
- Hata S., Satyanarayana K., Devlin P., Band H., McLean J., Strominger J. L., Brenner M. B., Krangel M. S. Extensive junctional diversity of rearranged human T cell receptor delta genes. Science. 1988 Jun 10;240(4858):1541–1544. doi: 10.1126/science.3259726. [DOI] [PubMed] [Google Scholar]
- Heisterkamp N., Stam K., Groffen J., de Klein A., Grosveld G. Structural organization of the bcr gene and its role in the Ph' translocation. 1985 Jun 27-Jul 3Nature. 315(6022):758–761. doi: 10.1038/315758a0. [DOI] [PubMed] [Google Scholar]
- Hershfield M. S., Kurtzberg J., Harden E., Moore J. O., Whang-Peng J., Haynes B. F. Conversion of a stem cell leukemia from a T-lymphoid to a myeloid phenotype induced by the adenosine deaminase inhibitor 2'-deoxycoformycin. Proc Natl Acad Sci U S A. 1984 Jan;81(1):253–257. doi: 10.1073/pnas.81.1.253. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hull M. T., Griep J. A. Mixed leukemia, lymphatic and myelomonocytic. Am J Clin Pathol. 1980 Oct;74(4):473–475. doi: 10.1093/ajcp/74.4.473. [DOI] [PubMed] [Google Scholar]
- Kirsch I. R., Brown J. A., Lawrence J., Korsmeyer S. J., Morton C. C. Translocations that highlight chromosomal regions of differentiated activity. Cancer Genet Cytogenet. 1985 Oct;18(2):159–171. doi: 10.1016/0165-4608(85)90066-4. [DOI] [PubMed] [Google Scholar]
- Kirsch I. R., Morton C. C., Nakahara K., Leder P. Human immunoglobulin heavy chain genes map to a region of translocations in malignant B lymphocytes. Science. 1982 Apr 16;216(4543):301–303. doi: 10.1126/science.6801764. [DOI] [PubMed] [Google Scholar]
- Kurtzberg J., Bigner S. H., Hershfield M. S. Establishment of the DU.528 human lymphohemopoietic stem cell line. J Exp Med. 1985 Nov 1;162(5):1561–1578. doi: 10.1084/jem.162.5.1561. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lawrence J. B., Villnave C. A., Singer R. H. Sensitive, high-resolution chromatin and chromosome mapping in situ: presence and orientation of two closely integrated copies of EBV in a lymphoma line. Cell. 1988 Jan 15;52(1):51–61. doi: 10.1016/0092-8674(88)90530-2. [DOI] [PubMed] [Google Scholar]
- Leder P., Battey J., Lenoir G., Moulding C., Murphy W., Potter H., Stewart T., Taub R. Translocations among antibody genes in human cancer. Science. 1983 Nov 18;222(4625):765–771. doi: 10.1126/science.6356357. [DOI] [PubMed] [Google Scholar]
- Mathieu-Mahul D., Bernheim A., Sigaux F., Daniel M. T., Larsen C. J., Berger R. Translocation t(1; 14) et remaniement du gène de la chaîne alpha du récepteur T dans une leucémie aiguë lymphoblastique T. C R Acad Sci III. 1986;302(14):525–528. [PubMed] [Google Scholar]
- Nicola N. A., Begley C. G., Metcalf D. Identification of the human analogue of a regulator that induces differentiation in murine leukaemic cells. Nature. 1985 Apr 18;314(6012):625–628. doi: 10.1038/314625a0. [DOI] [PubMed] [Google Scholar]
- Paietta E., Dutcher J. P., Wiernik P. H. Terminal transferase positive acute promyelocytic leukemia: in vitro differentiation of a T-lymphocytic/promyelocytic hybrid phenotype. Blood. 1985 Jan;65(1):107–114. [PubMed] [Google Scholar]
- Pui C. H., Dahl G. V., Melvin S., Williams D. L., Peiper S., Mirro J., Murphy S. B., Stass S. Acute leukaemia with mixed lymphoid and myeloid phenotype. Br J Haematol. 1984 Jan;56(1):121–130. doi: 10.1111/j.1365-2141.1984.tb01277.x. [DOI] [PubMed] [Google Scholar]
- Ruscetti F. W., Collins S. J., Woods A. M., Gallo R. C. Clonal analysis of the response of human myeloid leukemic cell lines to colony-stimulating activity. Blood. 1981 Aug;58(2):285–292. [PubMed] [Google Scholar]
- Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Selypes A., László A. A new translocation t(1;4;11) in congenital acute nonlymphocytic leukemia (acute myeloblastic leukemia). Hum Genet. 1987 May;76(1):106–108. doi: 10.1007/BF00283060. [DOI] [PubMed] [Google Scholar]
- Shtivelman E., Lifshitz B., Gale R. P., Canaani E. Fused transcript of abl and bcr genes in chronic myelogenous leukaemia. Nature. 1985 Jun 13;315(6020):550–554. doi: 10.1038/315550a0. [DOI] [PubMed] [Google Scholar]
- Smith S. D., Morgan R., Gemmell R., Amylon M. D., Link M. P., Linker C., Hecht B. K., Warnke R., Glader B. E., Hecht F. Clinical and biologic characterization of T-cell neoplasias with rearrangements of chromosome 7 band q34. Blood. 1988 Feb;71(2):395–402. [PubMed] [Google Scholar]
- Souza L. M., Boone T. C., Gabrilove J., Lai P. H., Zsebo K. M., Murdock D. C., Chazin V. R., Bruszewski J., Lu H., Chen K. K. Recombinant human granulocyte colony-stimulating factor: effects on normal and leukemic myeloid cells. Science. 1986 Apr 4;232(4746):61–65. doi: 10.1126/science.2420009. [DOI] [PubMed] [Google Scholar]
- Takihara Y., Champagne E., Griesser H., Kimura N., Tkachuk D., Reimann J., Okada A., Alt F. W., Chess L., Minden M. Sequence and organization of the human T cell delta chain gene. Eur J Immunol. 1988 Feb;18(2):283–287. doi: 10.1002/eji.1830180216. [DOI] [PubMed] [Google Scholar]
- Takihara Y., Tkachuk D., Michalopoulos E., Champagne E., Reimann J., Minden M., Mak T. W. Sequence and organization of the diversity, joining, and constant region genes of the human T-cell delta-chain locus. Proc Natl Acad Sci U S A. 1988 Aug;85(16):6097–6101. doi: 10.1073/pnas.85.16.6097. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Taub R., Kirsch I., Morton C., Lenoir G., Swan D., Tronick S., Aaronson S., Leder P. Translocation of the c-myc gene into the immunoglobulin heavy chain locus in human Burkitt lymphoma and murine plasmacytoma cells. Proc Natl Acad Sci U S A. 1982 Dec;79(24):7837–7841. doi: 10.1073/pnas.79.24.7837. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tsujimoto Y., Finger L. R., Yunis J., Nowell P. C., Croce C. M. Cloning of the chromosome breakpoint of neoplastic B cells with the t(14;18) chromosome translocation. Science. 1984 Nov 30;226(4678):1097–1099. doi: 10.1126/science.6093263. [DOI] [PubMed] [Google Scholar]
- Tsujimoto Y., Yunis J., Onorato-Showe L., Erikson J., Nowell P. C., Croce C. M. Molecular cloning of the chromosomal breakpoint of B-cell lymphomas and leukemias with the t(11;14) chromosome translocation. Science. 1984 Jun 29;224(4656):1403–1406. doi: 10.1126/science.6610211. [DOI] [PubMed] [Google Scholar]
- WHANG J., FREI E., 3rd, TJIO J. H., CARBONE P. P., BRECHER G. THE DISTRIBUTION OF THE PHILADELPHIA CHROMOSOME IN PATIENTS WITH CHRONIC MYELOGENOUS LEUKEMIA. Blood. 1963 Dec;22:664–673. [PubMed] [Google Scholar]
- Waldmann T. A. The arrangement of immunoglobulin and T cell receptor genes in human lymphoproliferative disorders. Adv Immunol. 1987;40:247–321. doi: 10.1016/s0065-2776(08)60241-2. [DOI] [PubMed] [Google Scholar]
- de Villartay J. P., Hockett R. D., Coran D., Korsmeyer S. J., Cohen D. I. Deletion of the human T-cell receptor delta-gene by a site-specific recombination. Nature. 1988 Sep 8;335(6186):170–174. doi: 10.1038/335170a0. [DOI] [PubMed] [Google Scholar]