Abstract
The specific (6;9)(p23;q34) chromosomal translocation is associated with a defined subtype of acute nonlymphocytic leukemia (ANLL). The 9q34 breakpoint is located at the telomeric side of the c-abl gene. Through a combination of chromosome jumping, long-range mapping, and chromosome walking, the chromosome 9 breakpoints of several t(6;9) ANLL patients were localized within a defined region of 8 kilobases (kb), 360 kb telomeric of c-abl. Subsequent cDNA cloning revealed that this region represented an intron in the middle of a gene, called Cain (can), encoding a 7.5-kb transcript. Disruption of the can gene by the translocation resulted in the expression of a new 5.5-kb can mRNA from the 6p- chromosome. Isolation of chromosome 6 sequences showed that breakpoints on 6p23 also clustered within a limited stretch of DNA. These data strongly suggest a direct involvement of the translocation in the leukemic process of t(6;9) ANLL.
Full text
PDFImages in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Adriaansen H. J., Guerts van Kessel A. H., Wijdenes-de Bresser J. H., van Drunen-Schoenmaker E., van Dongen J. J. Expression of the myeloid differentiation antigen CD33 depends on the presence of human chromosome 19 in human-mouse hybrids. Ann Hum Genet. 1990 May;54(Pt 2):115–119. doi: 10.1111/j.1469-1809.1990.tb00367.x. [DOI] [PubMed] [Google Scholar]
- Adriaansen H. J., van Dongen J. J., Hooijkaas H., Hählen K., van 't Veer M. B., Löwenberg B., Hagemeijer A. Translocation (6;9) may be associated with a specific TdT-positive immunological phenotype in ANLL. Leukemia. 1988 Mar;2(3):136–140. [PubMed] [Google Scholar]
- Auffray C., Rougeon F. Purification of mouse immunoglobulin heavy-chain messenger RNAs from total myeloma tumor RNA. Eur J Biochem. 1980 Jun;107(2):303–314. doi: 10.1111/j.1432-1033.1980.tb06030.x. [DOI] [PubMed] [Google Scholar]
- Ben-Neriah Y., Daley G. Q., Mes-Masson A. M., Witte O. N., Baltimore D. The chronic myelogenous leukemia-specific P210 protein is the product of the bcr/abl hybrid gene. Science. 1986 Jul 11;233(4760):212–214. doi: 10.1126/science.3460176. [DOI] [PubMed] [Google Scholar]
- Bird A. P. CpG-rich islands and the function of DNA methylation. Nature. 1986 May 15;321(6067):209–213. doi: 10.1038/321209a0. [DOI] [PubMed] [Google Scholar]
- Chen S. J., Chen Z., Grausz J. D., Hillion J., d'Auriol L., Flandrin G., Larsen C. J., Berger R. Molecular cloning of a 5' segment of the genomic phl gene defines a new breakpoint cluster region (bcr2) in Philadelphia-positive acute leukemias. Leukemia. 1988 Oct;2(10):634–641. [PubMed] [Google Scholar]
- Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
- Clare N., Boldt D., Messerschmidt G., Zeltzer P., Hansen K., Manhoff L. Lymphocyte malignancy and chromosome 14: structural aberrations involving band q11. Blood. 1986 Mar;67(3):704–709. [PubMed] [Google Scholar]
- Cleary M. L., Mellentin J. D., Spies J., Smith S. D. Chromosomal translocation involving the beta T cell receptor gene in acute leukemia. J Exp Med. 1988 Feb 1;167(2):682–687. doi: 10.1084/jem.167.2.682. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Croce C. M., Isobe M., Palumbo A., Puck J., Ming J., Tweardy D., Erikson J., Davis M., Rovera G. Gene for alpha-chain of human T-cell receptor: location on chromosome 14 region involved in T-cell neoplasms. Science. 1985 Mar 1;227(4690):1044–1047. doi: 10.1126/science.3919442. [DOI] [PubMed] [Google Scholar]
- Croce C. M., Shander M., Martinis J., Cicurel L., D'Ancona G. G., Dolby T. W., Koprowski H. Chromosomal location of the genes for human immunoglobulin heavy chains. Proc Natl Acad Sci U S A. 1979 Jul;76(7):3416–3419. doi: 10.1073/pnas.76.7.3416. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Domen J., Von Lindern M., Hermans A., Breuer M., Grosveld G., Berns A. Comparison of the human and mouse PIM-1 cDNAs: nucleotide sequence and immunological identification of the in vitro synthesized PIM-1 protein. Oncogene Res. 1987 Jun;1(1):103–112. [PubMed] [Google Scholar]
- Erikson J., Martinis J., Croce C. M. Assignment of the genes for human lambda immunoglobulin chains to chromosome 22. Nature. 1981 Nov 12;294(5837):173–175. doi: 10.1038/294173a0. [DOI] [PubMed] [Google Scholar]
- 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]
- Frischauf A. M., Lehrach H., Poustka A., Murray N. Lambda replacement vectors carrying polylinker sequences. J Mol Biol. 1983 Nov 15;170(4):827–842. doi: 10.1016/s0022-2836(83)80190-9. [DOI] [PubMed] [Google Scholar]
- Grosveld G., Verwoerd T., van Agthoven T., de Klein A., Ramachandran K. L., Heisterkamp N., Stam K., Groffen J. The chronic myelocytic cell line K562 contains a breakpoint in bcr and produces a chimeric bcr/c-abl transcript. Mol Cell Biol. 1986 Feb;6(2):607–616. doi: 10.1128/mcb.6.2.607. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hariharan I. K., Harris A. W., Crawford M., Abud H., Webb E., Cory S., Adams J. M. A bcr-v-abl oncogene induces lymphomas in transgenic mice. Mol Cell Biol. 1989 Jul;9(7):2798–2805. doi: 10.1128/mcb.9.7.2798. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hecht F., Morgan R., Gemmill R. M., Hecht B. K. Translocations in T-cell leukemia in lymphoma. N Engl J Med. 1985 Sep 19;313(12):758–759. doi: 10.1056/NEJM198509193131218. [DOI] [PubMed] [Google Scholar]
- Heim S., Kristoffersson U., Mandahl N., Mitelman F., Bekassy A. N., Garwicz S., Wiebe T. High resolution banding analysis of the reciprocal translocation t(6;9) in acute nonlymphocytic leukemia. Cancer Genet Cytogenet. 1986 Jul;22(3):195–201. doi: 10.1016/0165-4608(86)90155-x. [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]
- Heisterkamp N., Stephenson J. R., Groffen J., Hansen P. F., de Klein A., Bartram C. R., Grosveld G. Localization of the c-ab1 oncogene adjacent to a translocation break point in chronic myelocytic leukaemia. Nature. 1983 Nov 17;306(5940):239–242. doi: 10.1038/306239a0. [DOI] [PubMed] [Google Scholar]
- Hermans A., Heisterkamp N., von Linden M., van Baal S., Meijer D., van der Plas D., Wiedemann L. M., Groffen J., Bootsma D., Grosveld G. Unique fusion of bcr and c-abl genes in Philadelphia chromosome positive acute lymphoblastic leukemia. Cell. 1987 Oct 9;51(1):33–40. doi: 10.1016/0092-8674(87)90007-9. [DOI] [PubMed] [Google Scholar]
- Isobe M., Erikson J., Emanuel B. S., Nowell P. C., Croce C. M. Location of gene for beta subunit of human T-cell receptor at band 7q35, a region prone to rearrangements in T cells. Science. 1985 May 3;228(4699):580–582. doi: 10.1126/science.3983641. [DOI] [PubMed] [Google Scholar]
- Jeffreys A. J., Flavell R. A. A physical map of the DNA regions flanking the rabbit beta-globin gene. Cell. 1977 Oct;12(2):429–439. doi: 10.1016/0092-8674(77)90119-2. [DOI] [PubMed] [Google Scholar]
- Kaneko Y., Frizzera G., Maseki N., Sakurai M., Komada Y., Sakurai M., Hiyoshi Y., Nakadate H., Takeda T. A novel translocation, t(9;17)(q34;q23), in aggressive childhood lymphoblastic lymphoma. Leukemia. 1988 Nov;2(11):745–748. [PubMed] [Google Scholar]
- Kaneko Y., Variakojis D., Kluskens L., Rowley J. D. Lymphoblastic lymphoma: cytogenetic, pathologic, and immunologic studies. Int J Cancer. 1982 Sep 15;30(3):273–279. doi: 10.1002/ijc.2910300304. [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]
- Konopka J. B., Watanabe S. M., Witte O. N. An alteration of the human c-abl protein in K562 leukemia cells unmasks associated tyrosine kinase activity. Cell. 1984 Jul;37(3):1035–1042. doi: 10.1016/0092-8674(84)90438-0. [DOI] [PubMed] [Google Scholar]
- Kurzrock R., Gutterman J. U., Talpaz M. The molecular genetics of Philadelphia chromosome-positive leukemias. N Engl J Med. 1988 Oct 13;319(15):990–998. doi: 10.1056/NEJM198810133191506. [DOI] [PubMed] [Google Scholar]
- Malcolm S., Barton P., Murphy C., Ferguson-Smith M. A., Bentley D. L., Rabbitts T. H. Localization of human immunoglobulin kappa light chain variable region genes to the short arm of chromosome 2 by in situ hybridization. Proc Natl Acad Sci U S A. 1982 Aug;79(16):4957–4961. doi: 10.1073/pnas.79.16.4957. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McLaughlin J., Chianese E., Witte O. N. Alternative forms of the BCR-ABL oncogene have quantitatively different potencies for stimulation of immature lymphoid cells. Mol Cell Biol. 1989 May;9(5):1866–1874. doi: 10.1128/mcb.9.5.1866. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McLaughlin J., Chianese E., Witte O. N. In vitro transformation of immature hematopoietic cells by the P210 BCR/ABL oncogene product of the Philadelphia chromosome. Proc Natl Acad Sci U S A. 1987 Sep;84(18):6558–6562. doi: 10.1073/pnas.84.18.6558. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mellentin J. D., Smith S. D., Cleary M. L. lyl-1, a novel gene altered by chromosomal translocation in T cell leukemia, codes for a protein with a helix-loop-helix DNA binding motif. Cell. 1989 Jul 14;58(1):77–83. doi: 10.1016/0092-8674(89)90404-2. [DOI] [PubMed] [Google Scholar]
- Nagarajan L., Louie E., Tsujimoto Y., ar-Rushdi A., Huebner K., Croce C. M. Localization of the human pim oncogene (PIM) to a region of chromosome 6 involved in translocations in acute leukemias. Proc Natl Acad Sci U S A. 1986 Apr;83(8):2556–2560. doi: 10.1073/pnas.83.8.2556. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nishikura K., ar-Rushdi A., Erikson J., Watt R., Rovera G., Croce C. M. Differential expression of the normal and of the translocated human c-myc oncogenes in B cells. Proc Natl Acad Sci U S A. 1983 Aug;80(15):4822–4826. doi: 10.1073/pnas.80.15.4822. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pearson M. G., Vardiman J. W., Le Beau M. M., Rowley J. D., Schwartz S., Kerman S. L., Cohen M. M., Fleischman E. W., Prigogina E. L. Increased numbers of marrow basophils may be associated with a t(6;9) in ANLL. Am J Hematol. 1985 Apr;18(4):393–403. doi: 10.1002/ajh.2830180409. [DOI] [PubMed] [Google Scholar]
- Poustka A., Pohl T. M., Barlow D. P., Frischauf A. M., Lehrach H. Construction and use of human chromosome jumping libraries from NotI-digested DNA. Nature. 1987 Jan 22;325(6102):353–355. doi: 10.1038/325353a0. [DOI] [PubMed] [Google Scholar]
- Rabbitts T. H., Lefranc M. P., Stinson M. A., Sims J. E., Schroder J., Steinmetz M., Spurr N. L., Solomon E., Goodfellow P. N. The chromosomal location of T-cell receptor genes and a T cell rearranging gene: possible correlation with specific translocations in human T cell leukaemia. EMBO J. 1985 Jun;4(6):1461–1465. doi: 10.1002/j.1460-2075.1985.tb03803.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Reynolds T. C., Smith S. D., Sklar J. Analysis of DNA surrounding the breakpoints of chromosomal translocations involving the beta T cell receptor gene in human lymphoblastic neoplasms. Cell. 1987 Jul 3;50(1):107–117. doi: 10.1016/0092-8674(87)90667-2. [DOI] [PubMed] [Google Scholar]
- Selden J. R., Emanuel B. S., Wang E., Cannizzaro L., Palumbo A., Erikson J., Nowell P. C., Rovera G., Croce C. M. Amplified C lambda and c-abl genes are on the same marker chromosome in K562 leukemia cells. Proc Natl Acad Sci U S A. 1983 Dec;80(23):7289–7292. doi: 10.1073/pnas.80.23.7289. [DOI] [PMC free article] [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]
- 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]
- Walker L. C., Ganesan T. S., Dhut S., Gibbons B., Lister T. A., Rothbard J., Young B. D. Novel chimaeric protein expressed in Philadelphia positive acute lymphoblastic leukaemia. 1987 Oct 29-Nov 4Nature. 329(6142):851–853. doi: 10.1038/329851a0. [DOI] [PubMed] [Google Scholar]
- Westbrook C. A., Le Beau M. M., Diaz M. O., Groffen J., Rowley J. D. Chromosomal localization and characterization of c-abl in the t(6;9) of acute nonlymphocytic leukemia. Proc Natl Acad Sci U S A. 1985 Dec;82(24):8742–8746. doi: 10.1073/pnas.82.24.8742. [DOI] [PMC free article] [PubMed] [Google Scholar]
- de Klein A., van Agthoven T., Groffen C., Heisterkamp N., Groffen J., Grosveld G. Molecular analysis of both translocation products of a Philadelphia-positive CML patient. Nucleic Acids Res. 1986 Sep 11;14(17):7071–7082. doi: 10.1093/nar/14.17.7071. [DOI] [PMC free article] [PubMed] [Google Scholar]
- van der Feltz M. J., Shivji M. K., Grosveld G., Wiedemann L. M. Characterization of the translocation breakpoint in a patient with Philadelphia positive, bcr negative acute lymphoblastic leukaemia. Oncogene. 1988 Aug;3(2):215–219. [PubMed] [Google Scholar]
- von Lindern M., van Agthoven T., Hagemeijer A., Adriaansen H., Grosveld G. The human pim-1 gene is not directly activated by the translocation (6;9) in acute nonlymphocytic leukemia. Oncogene. 1989 Jan;4(1):75–79. [PubMed] [Google Scholar]