Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Manuscript
  • Published:

Disruption of the RanBP17/Hox11L2 region by recombination with the TCRδ locus in acute lymphoblastic leukemias with t(5;14)(q34;q11)

Leukemia volume 16, pages 2205–2212 (2002)Cite this article

Abstract

The t(5;14)(q33-34;q11) translocation constitutes a recurrent rearrangement in acute lymphoblastic leukemia involving the T cell receptor (TCR) δ locus on chromosome 14. Breakpoint sequences of the derivative chromosome 5 were isolated by application of a ligation-mediated PCR technique using TCR δ-specific primers to amplify genomic DNA from the leukemic cells of a patient with t(5;14). Through exon trap analysis, we identified various putative exons of the chromosome 5 target gene of the translocation; compilation of sequence information of trapped exons and available expressed sequence tags (ESTs) from the GenBank database allowed us to assemble 1.2 kb of the cDNA. Full-length cDNAs were isolated from a human testis cDNA library and sequence analysis predicted a putative Ran binding protein, a novel member of the importin-β superfamily of nuclear transport receptors, called RanBP17. The t(5;14) breakpoint maps to the 3′ coding region of the gene. The breakpoint of a second t(5;14) positive patient was mapped about 8 kb downstream of the most 3′ RanBP17 exon and 2 kb upstream of the first exon of the orphan homeobox gene, Hox11L2. In both cases TCR δ enhancer sequences are juxtaposed downstream of the truncated or intact RanBP17 gene, respectively on the derivative chromosome.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5

Similar content being viewed by others

References

  1. Klein G . Immunoglobulin gene-associated chromosomal translocations in B-cell derived tumors Curr Top Microbiol Immunology 1999 246: 161–167

    CAS  Google Scholar 

  2. Rabbitts TH . Chromosomal translocations in human cancer Nature 1994 372: 143–149

    Article  CAS  PubMed  Google Scholar 

  3. Look AT . Oncogenic transcription factors in the human acute leukemias Science 1997 278: 1059–1064

    Article  CAS  PubMed  Google Scholar 

  4. Janssen JWG, Vaandrager J-W, Heuser T, Jauch A, Kluin PM, Geelen E, Bergsagel PL, Kuehl WM, Drexler HG, Otsuki T, Bartram CR, Schuuring E . Concurrent activation of a novel putative transforming gene, myeov, and cyclinD1 in a subset of multiple myeloma cell lines with t(11;14)(q13;q32) Blood 2000 95: 2691–2698

    CAS  PubMed  Google Scholar 

  5. Willis TG, Jadayel DM, Du M-Q, Peng H, Perry AR, Abdul-Rauf M, Price H, Karran L, Majekodunmi O, Wlodarska I, Pan L, Crook T, Hamoudi R, Isaacson PG, Dyer . Bcl10 is involved in t(1;14)(p22;q32) of MALT B Cell lymphoma and mutated in multiple tumor types Cell 1999 96: 35–45

    Article  CAS  PubMed  Google Scholar 

  6. Zhang Q, Siebert R, Yan M, Hinzmann B, Cui X, Xue L, Rakestraw KM, Naeve CW, Beckmann G, Weisenburger DD, Sanger WG, Nowotny H, Vesely M, Callet-Bauchu E, Salles G, Dixit VM, Rosenthal A, Schlegelberger B, Morris SW . Inactivating mutations and overexpression of BCL10, a caspase recruitment domain-containing gene, in MALT lymphoma with t(1;14)(p22;q32) Nat Genet 1999 22: 63–68

    Article  CAS  PubMed  Google Scholar 

  7. Richelda R, Ronchetti D, Baldini L, Cro L, Viggiano L, Marzella R, Rocchi M, Otsuki T, Lombardi L, Maiolo AT, Neri A . A novel chromosomal translocation t(4;14)(p16.3;q32) in multiple myeloma involves the fibroblast growth-factor receptor 3 gene Blood 1997 90: 4062–4070

    CAS  PubMed  Google Scholar 

  8. Chesi M, Nardini E, Brents LA, Schrock E, Ried T, Kuehl WM, Bergsagel PL . Frequent translocation t(4;14)(p16.3;q32.3) in multiple myeloma is associated with increased expression and activating mutations of fibroblast growth factor receptor 3 Nat Genet 1997 16: 260–264

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Whitlock JA, Raimondi SC, Harbott J, Morris SW, McCurley TL, Hansen-Hagge TE, Ludwig WD, Weimann G, Bartram CR . t(5;14)(q33-34;q11), a new recurring cytogenetic abnormality in childhood acute leukemia Leukemia 1994 8: 1539–1543

    CAS  PubMed  Google Scholar 

  10. Janssen JWG, Braunger J, Ballas K, Faust M, Siebers U, Steenvoorden ACM, Bartram CR . Spectrum of transforming sequences detected by tumorigenicity assay in a large series of human neoplasms Int J Cancer 1999 80: 857–862

    Article  CAS  PubMed  Google Scholar 

  11. Boehm T, Baer R, Lavenir I, Forster A, Waters JJ, Nacheva E, Rabbitts TH . The mechanism of chromosomal translocation t(11;14) involving the T cell receptor C delta locus on human chromosome 14q11 and a transcribed region of chromosome 11p15 EMBO J 1988 7: 385–394

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Sealey PG, Whittaker PA, Southern EM . Removal of repeated sequences from hybridisation probes Nucleic Acids Res 1985 13: 1905–1922

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Chomczynski P, Sacchi N . Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction Anal Biochem 1987 162: 156–159

    Article  CAS  PubMed  Google Scholar 

  14. Shackleford GM, Varmus HE . Expression of the proto-oncogene int-1 is restricted to postmeiotic male germ cells and the neural tube of mid-gestational embryos Cell 1987 50: 89–95

    Article  CAS  PubMed  Google Scholar 

  15. Natarajan D, Boulter CA . Isolation of genomic sequences flanking a retroviral insertion site using a novel PCR-based method Gene 1995 161: 195–198

    Article  CAS  PubMed  Google Scholar 

  16. Davis LG, Dibner MD, Battey JF . Cloning DNA from the Eukaryotic Genome In: Davis LG, Dibner MD, Battey JF (eds) Basic Methods in Molecular Biology Elsevier: New York 1986 pp 167–191

    Google Scholar 

  17. Hansen-Hagge TE, Janssen JWG, Hameister H, Papa FR, Zechner U, Seriu T, Jauch A, Becke D, Hochstrasser M, Bartram CR . An evolutionarily conserved gene on human chromosome 5q33-q34, UBH1, encodes a novel deubiquitinating enzyme Genomics 1998 49: 411–418

    Article  CAS  PubMed  Google Scholar 

  18. Auch D, Reth M . Exon trap cloning: using PCR to rapidly detect and clone exons from genomic DNA fragments Nucleic Acids Res 1990 18: 6743–6744

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Nehls M, Pfeifer D, Boehm T . Exon amplification from complete libraries of genomic DNA using a novel phage vector with automatic plasmid excision facility: application to the mouse neurofibromatosis-1 locus Oncogene 1994 9: 2169–2175

    CAS  PubMed  Google Scholar 

  20. Saiki RK, Gelfand DH, Stoffel S, Scharf SJ, Higushi R, Horn GT, Mullis KB, Erlich HA . Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase Science 1988 239: 487–491

    Article  CAS  PubMed  Google Scholar 

  21. Hansen-Hagge TE, Yokota S, Reuter HJ, Schwarz K, Bartram CR . Human common acute lymphoblastic leukemia-derived cell lines are competent to recombine their T cell receptor delta/alpha regions along a hierarchically ordered pathway Blood 1992 80: 2353–2362

    CAS  PubMed  Google Scholar 

  22. Furano AV, Usdin K . DNA ‘fossils’ and phylogenetic analysis. Using L1 (LINE-1, long interspersed repeated) DNA to determine the evolutionary history of mammals J Biol Chem 1995 270: 25301–25304

    Article  CAS  PubMed  Google Scholar 

  23. Koch P, Bohlmann I, Schäfer M, Hansen-Hagge TE, Kiyoi H, Wilda M, Hameister H, Bartram CR, Janssen JWG . Identification of a novel putative Ran binding protein and its close homologue Biochem Biophys Res Commun 2000 278: 241–249

    Article  CAS  PubMed  Google Scholar 

  24. Kozak M . Interpreting cDNA sequences: some insights from studies on translation Mamm Genome 1996 7: 563–574

    Article  CAS  PubMed  Google Scholar 

  25. Görlich D, Kutay U . Transport between the cell nucleus and the cytoplasm Annu Rev Cell Dev Biol 1999 15: 607–660

    Article  PubMed  Google Scholar 

  26. Watson A, Smaldon N, Lucke R, Hawkins T . The Caenorhabditis elegans genome sequencing project: first steps in automation Nature 1993 362: 569–570

    Article  CAS  PubMed  Google Scholar 

  27. Yancopoulos GD, DePinho RA, Zimmerman KA, Lutzker SG, Rosenberg N, Alt FW . Secondary genomic rearrangement events in pre-B cells: VHDJH replacement by a LINE-1 sequence and directed class switching EMBO J 1986 5: 3259–3266

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Pear WS, Nelson SF, Axelson H, Wahlstrom G, Bazin H, Klein G, Sumegi J . Aberrant class switching juxtaposes c-myc with a middle repetitive element (LINE) and an IgH intron in two spontaneously arising rat immunocytomas Oncogene 1988 2: 499–507

    CAS  PubMed  Google Scholar 

  29. Rabbitts PH, Douglas J, Fischer P, Nacheva E, Karpas A, Catovsky D, Melo JV, Baer R, Stinson MA, Rabbitts TH . Chromosome abnormalities at 11q13 in B cell tumours Oncogene 1988 3: 99–103

    CAS  Google Scholar 

  30. Von Lindern M, Breems D, van Baal S, Adriaansen H, Grosveld G . Characterization of the translocation breakpoint sequences of two DEK-CAN fusion genes present in t(6;9) acute myeloid leukemia and a SET-CAN fusion gene found in a case of acute undifferentiated leukemia Genes Chromosom Cancer 1992 5: 227–234

    Article  CAS  PubMed  Google Scholar 

  31. Miki Y, Nishisho I, Horii A, Miyoshi Y, Utsunomiya J, Kinzler KW, Vogelstein B, Nakamura Y . Disruption of the APC gene by a retrotransposal insertion of L1 sequence in a colon cancer Cancer Res 1992 52: 643–645

    CAS  PubMed  Google Scholar 

  32. Toriello HV, Glover TW, Takahara K, Byers PH, Miller DE, Higgins JV, Greenspan DS . A translocation interrupts the COL5A1 gene in a patient with Ehlers-Danlos syndrome and hypomelanosis of Ito Nat Genet 1996 13: 361–365

    Article  CAS  PubMed  Google Scholar 

  33. Drechsler M, Royer-Pokora B . A LINE element present at the site of a 300-kb deletion starting in intron 10 of the PAX6 gene in a case of familial aniridia Hum Genet 1996 98: 297–303

    Article  CAS  PubMed  Google Scholar 

  34. Van de Water N, Williams R, Ockelford P, Browett P . A 20.7 kb deletion within the factor VIII gene associated with LINE-1 element insertion Thromb Haemost 1998 79: 938–942

    CAS  PubMed  Google Scholar 

  35. Kumatori A, Faizunnessa NN, Suzuki S, Moriuchi T, Kurozumi H, Nakamura M . Nonhomologous recombination between the cytochrome b558 heavy chain gene (CYBB) and LINE-1 causes an X-linked chronic granulomatous disease Genomics 1998 53: 123–128

    Article  CAS  PubMed  Google Scholar 

  36. Segal Y, Peissel B, Renieri A, de Marchi M, Ballabio A, Pei Y, Zhou J . LINE-1 elements at the sites of molecular rearrangements in Alport syndrome-diffuse leiomyomatosis Am J Hum Genet 1999 64: 62–69

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Stochaj U, Rother KL . Nucleocytoplasmic trafficking of proteins: with or without Ran? BioEssays 1999 21: 579–589

    Article  Google Scholar 

  38. Nakielny S, Dreyfuss G . Transport of proteins and RNAs in and out of the nucleus Cell 1999 99: 677–690

    Article  CAS  PubMed  Google Scholar 

  39. Kraemer D, Wozniak RW, Blobel G, Radu A . The human CAN protein, a putative oncogene product associated with myeloid leukemogenesis, is a nuclear pore complex protein that faces the cytoplasm Proc Natl Acad Sci USA 1994 91: 1519–1523

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Borrow J, Shearman AM, Stanton VP, Becher R, Collins T, Williams AJ, Dube I, Katz F, Kwong YL, Morris C, Ohyashiki K, Toyama K, Rowley J, Housman DE . The t(7;11)(p15;p15) translocation in acute myeloid leukemia fuses the genes for nucleoporin NUP98 and class 1 homeoprotein HOXA9 Nat Genet 1996 12: 159–167

    Article  CAS  PubMed  Google Scholar 

  41. Nakamura T, Largaespada DA, Lee MP, Johnson LA, Ohyashiki K, Toyama K, Chen SJ, Willman CL, Chen IM, Feinberg AP, Jenkins NA, Copeland NG, Shaughnessy JD . Fusion of the nucleoporin gene NUP98 to HOXA9 by the chromosome translocation t(7;11)(p15;p15) in human myeloid leukemia Nat Genet 1996 12: 154–158

    Article  CAS  PubMed  Google Scholar 

  42. Raza-Egilmez SZ, Jani-Sait SN, Grossi M, Higgins MJ, Shows TB, Aplan PD . NUP98-HOXD13 gene fusion in therapy-related acute myelogenous leukemia Cancer Res 1998 58: 4269–4273

    CAS  PubMed  Google Scholar 

  43. Arai Y, Hosoda F, Kobayashi H, Arai K, Hayashi Y, Kamada N, Kaneko Y, Ohki M . The inv(11)(p15q22) chromosome translocation of de novo and therapy-related myeloid malignancies results in fusion of the nucleoporin gene, NUP98, with the putative RNA helicase, DDX10 Blood 1997 89: 3936–3944

    CAS  PubMed  Google Scholar 

  44. Nakamura T, Yamazaki Y, Hatano Y, Miura I . NUP98 is fused to PMX1 homeobox gene in human acute myelogenous leukemia with chromosome translocation t(1;11)(q23;p15) Blood 1999 94: 741–747

    CAS  PubMed  Google Scholar 

  45. Hussey DJ, Nicola M, Moore S, Peters GB, Dobrovic A . The t(4;11)(q21;p15) translocation fuses the NUP98 and RAP1GADS1 genes and is recurrent in T cell acute lymphocytic leukemia Blood 1999 94: 2072–2079

    CAS  PubMed  Google Scholar 

  46. Buske C, Humphries RK . Homeobox genes in leukemogenesis Int J Hematol 2000 71: 301–308

    CAS  PubMed  Google Scholar 

  47. Bernard OA, Busson-LeConiat M, Ballerini P, Mauchauffé M, Della Valle V, Monni R, Nguyen Khac F, Mercher T, Penard-Lacronique V, Pasturaud P, Gressin L, Heilig R, Daniel M-T, Lessard M, Berger R . A new recurrent and specific cryptic translocation, t(5;14)(q35;q32), is associated with expression of the Hox11L2 gene in T acute lymphoblastic leukemia Leukemia 2001 15: 1495–1504

    Article  CAS  PubMed  Google Scholar 

  48. Bhoem T, Foroni L, Kaneko Y, Perutz MF, Rabbitts TH . The rhombotin family of cysteine-rich LIM-domain oncogenes: distinct members are involved in T cell translocations to human chromosomes 11p15 and 11p13 Proc Natl Acad Sci USA 1991 88: 4367–4371

    Article  Google Scholar 

  49. Royer-Pokora B, Rogers M, Zhu TH, Schneider S, Loos U, Bolitz U . The TTG-2/RBTN2 T cell oncogene encodes two alternative transcripts from two promoters: the distal promoter is removed by most 11p13 translocations in acute T cell leukemia′s (T-ALL) Oncogene 1995 10: 1353–1360

    CAS  PubMed  Google Scholar 

  50. Ferrando AA, Neuberg DS, Staunton J, Loh ML, Huard C, Raimondi SC, Behm FG, Pui C-H, Downing JR, Gilliland DG, Lander ES, Golub TR, Look AT . Gene expression signatures define novel oncogenic pathways in T cell acute lymphoblastic leukemia Cancer Cell 2002 1: 75–87

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This study was supported by grants from the European Community (EH 5th Framework Program-Quality of Life and Management of Living Resources; The Consortium Haematopoiesis & Cancer), from the Dr Mildred Scheel Stiftung für Krebsforschung (10-1253) to JWGJ and from the Deutsche Forschungsgemeinschaft to JWGJ and CRB, respectively. Supported also by National Cancer Institute grants CA76301 and CA69129 (to SWM) and Cancer Center Support (core) grant CA27165, and by the American Lebanese Syrian Associated Charities, St Jude Children′s Research Hospital. We are grateful to Christel Tell, Ulrike Spadinger, Daniela Becke, Magda Dietl, Dorothé Erz, Xiaoli Cui, and Yvonne Stark for their excellent technical assistance.

Author information

Author notes

  1. TE Hansen-Hagge, M Schäfer and H Kiyoi: The first three authors contributed equally to this work

Authors and Affiliations

  1. Department of Pediatrics II, University of Ulm, Section of Molecular Biology, Ulm, Germany

    TE Hansen-Hagge, H Kiyoi, C Mahotka, CR Bartram & JWG Janssen

  2. University of Heidelberg, Institute of Human Genetics, Heidelberg, Germany

    M Schäfer, P Koch, I Bohlmann, CR Bartram & JWG Janssen

  3. Department of Pathology, St Jude Children′s Research Hospital, Memphis, TN, USA

    SW Morris

  4. Division of Pediatric Hematology-Oncology, Vanderbilt University Medical Center, Nashville, TN, USA

    JA Whitlock

  5. Department of Dermatology, Humboldt University, Medical Faculty–Charité, Schumannstrasse 20/21, Berlin, D-10117, Germany

    TE Hansen-Hagge

  6. Department of Infectious Diseases, Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8560, Japan

    H Kiyoi

  7. Institut für Pathologie, Medizinische Einrichtungen der Heinrich Heine Universität, Moorenstr 5, Geb 14.79, Raum 316, Düsseldorf, D-40225, Germany

    C Mahotka

Authors
  1. TE Hansen-Hagge
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M Schäfer
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. H Kiyoi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. SW Morris
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. JA Whitlock
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. P Koch
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. I Bohlmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. C Mahotka
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. CR Bartram
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. JWG Janssen
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hansen-Hagge, T., Schäfer, M., Kiyoi, H. et al. Disruption of the RanBP17/Hox11L2 region by recombination with the TCRδ locus in acute lymphoblastic leukemias with t(5;14)(q34;q11). Leukemia 16, 2205–2212 (2002). https://doi.org/10.1038/sj.leu.2402671

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.leu.2402671

Keywords

This article is cited by

Search

Advanced search

Quick links