Skip to main content
SpringerLink
Log in

EB-1, a tyrosine kinase signal transduction gene, is transcriptionally activated in the t(1;19) subset of pre-B ALL, which express oncoprotein E2a-Pbx1

  • Original Paper
  • Published:
Oncogene Submit manuscript

Abstract

The t(1;19) translocation of pre-B cell acute lymphocytic leukemia (ALL) produces E2a-Pbx1, a chimeric oncoprotein containing the transactivation domains of E2a joined to the homeodomain protein, Pbx1. E2a-Pbx1 causes T cell and myeloid leukemia in mice, blocks differentiation of cultured myeloid progenitors, and transforms fibroblasts through a mechanism accompanied by aberrant expression of tissue-specific and developmentally-regulated genes. Here we investigate whether aberrant gene expression also occurs specifically in the t(1;19)-containing subset of pre-B cell ALL in man. Two new genes, EB-1 and EB-2, as well as Caldesmon were transcriptionally activated in each of seven t(1;19) cell lines. EB-1 expression was extremely low in marrow from patients having pre-B ALL not associated with the t(1;19), and elevated more than 100-fold in marrow from patients with pre-B ALL associated with the t(1;19). Normal EB-1 expression was strong in brain and testis, the same tissues exhibiting the highest levels of PBX1 expression. EB-1 encodes a signaling protein containing a phosphotyrosine binding domain homologous to that of dNumb developmental regulators and two SAM domains homologous to those in the C-terminal tail of Eph receptor tyrosine kinases. We conclude that aberrant expression of tissue-specific genes is a characteristic of t(1;19) pre-B ALL, as was previously found in fibroblasts transformed by E2a-Pbx1. Potentially, EB-1 overexpression could interfere with normal signaling controlling proliferation or differentiation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5

Similar content being viewed by others

References

  • Barr MM, Tu H, Van Aelst L and Wigler M. . 1996 Mol. Cell. Biol. 16: 5597–5603.

  • Bejsovec A and Wieschaus E. . 1993 Development 119: 501–517.

  • Campos-Ortega JA. . 1996 Neuron 17: 1–4.

  • Carroll A, Crist W, Parmley R, Roper M, Cooper M and Finley W. . 1984 Blood 63: 721–724.

  • Chan SK and Mann RS. . 1996 Proc. Natl. Acad. Sci. USA 93: 5223–5228.

  • Chang CP, Brocchieri L, Shen WF, Largman C and Cleary ML. . 1996 Mol. Cell. Biol. 16: 1734–1745.

  • Charite J, Graaff W, Shen S and Deschamps J. . 1994 Cell 78: 589–601.

  • Chisaka O and Capecchi M. . 1991 Nature 350: 473–479.

  • Chomczynski P and Sacchi N. . 1987 Anal. Biochem. 162: 156–159.

  • Davies BR, Davies MP, Gibbs FE, Barraclough R and Rudland PS. . 1993 Oncogene 8: 999–1008.

  • Dedera DA, Waller EK, Lebrun DP, Sen-Majumdar A, Stevens ME, Barsh GS and Cleary ML. . 1993 Cell 74: 833–843.

  • De Lau WB, Hurenkamp J, Berendes P, Touw IP, Clevers HC and van Dijk MA. . 1998 Oncogene 17: 503–510.

  • De Silva R, Englezou A, Schevzov G, Gerwin BI, Harris CC, Gunning P and Reddel RR. . 1994 Cell Mol. Biol. Res. 40: 323–335.

  • Feldman BJ, Reid T and Clear ML. . 1997 Oncogene 15: 2735–2742.

  • Fu X and Kamps MP. . 1997 Mol. Cell. Biol. 17: 1503–1512.

  • Green JA, Carthew P, Heuillet E, Simpson JL and Manson MM. . 1990 Carcinogenesis 11: 1175–1182.

  • Guo M, Jan LY and Jan YN. . 1996 Neuron 17: 27–41.

  • Hisano T, Ono M, Nakayama M, Naito S, Kuwano M and Wada M. . 1996 FEBS Lett. 397: 101–107.

  • Hubank M and Schatz D. . 1994 Nucl. Acid Res. 22: 5640–5648.

  • Inada T, Iwama A, Sakano S, Ohno M, Sawada K and Suda T. . 1997 Blood 89: 2757–2765.

  • Kamps MP, Murre C, Sun X and Baltimore D. . 1990 Cell 60: 547–555.

  • Kamps MP, Look T and Baltimore D. . 1991 Genes Dev. 5: 358–368.

  • Kamps MP and Baltimore D. . 1993 Mol. Cell. Biol. 13: 351–357.

  • Kamps MP and Wright D. . 1994 Oncogene 9: 3159–3166.

  • Kamps MP, Wright DD and Lu Q. . 1996 Oncogene 12: 19–30.

  • Kiyokawa E, Takai S, Tanaka M, Iwase T, Suzuki M, Xiang YY, Naito Y, Yamada K, Sugimura H and Kino I. . 1994 Cancer Res. 54: 3645–3650.

  • Klampfer L, Zhang J, Zelenetz A, Uchida H and Nimer SD. . 1996 Proc. Natl. Acad. Sci. USA 93: 14059–14064.

  • Knoepfler PS, Lu Q and Kamps MP. . 1996 Nucl. Acids Res. 24: 2288–2294.

  • Lebrun DP and Cleary ML. . 1994 Oncogene 9: 1641–1647.

  • Lee SB, Kolquist KA, Nichols K, Englert C, Maheswaran S, Ladanyi M, Gerald WL and Haber DA. . 1997 Nature Genet. 17: 309–313.

  • Lisitsyn N, Lisitsyn N and Wigler M. . 1993 Science 259: 946–951.

  • Lu Q, Wright DD and Kamps MP. . 1994 Mol. Cell. Biol. 14: 3938–3948.

  • Lu Q and Kamps MP. . 1997 Oncogene 14: 75–83.

  • Magni M, Shammah S, Schiró R, Mellado W, Dalla-Favera R and Gianni AM. . 1996 Blood 87: 1097–1103.

  • May, WA, Arvand A, Thompson AD, Braun BS, Wright M and Denny CT. . 1997 Nature Genet. 17: 495–497.

  • McWhirter JR, Goulding M, Weiner JA, Chun J and Murre C. . 1997 Development 124: 3221–3232.

  • Monica K, Galili N, Nourse J, Saltman D and Cleary ML. . 1991 Mol. Cell. Biol. 11: 6149–6157.

  • Nakamura T, Largaespada DA, Shaughnessy JD, Jenkins NA and Copeland NG. . 1996 Nature Gen. 12: 149–153.

  • Nourse J, Mellentin JD, Galili N, Wilkinson J, Stanbridge E, Smith SD and Cleary ML. . 1990 Cell 60: 535–545.

  • Rauskolb C, Peifer M and Wieschaus E. . 1993 Cell 74: 1101–1112.

  • Roberts VJ, van Dijk MA and Murre C. . 1995 Mech. Develop. 51: 193–198.

  • Sakane F, Imai S, Kai M, Wada I and Kanoh H. . 1996 J. Biol. Chem. 14: 8394–8401.

  • Schultz J, Ponting PP, Hofman K and Bork P. . 1997 Protein Science 6: 249–253.

  • Sakane F and Kanoh H. . 1997 Intn. J. Biochem. Cell Biol. 29: 1139–1143.

  • Sefton M and Nieto MA. . 1997 Cell Tiss. Res. 290: 243–250.

  • Smith KS, Jacobs Y, Chang CP and Cleary ML. . 1997 Oncogene 14: 2917–2926.

  • Stein E, Cerretti DP and Daniel TO. . 1996 J. Biol. Chem. 271: 23588–23593.

  • Surgucheva I and Bryan J. . 1995 Cell Motil. Cyto. 32: 233–243.

  • Tanaka S, Ouchi T and Hanafusa H. . 1997 Proc. Natl. Acad. Sci. USA 94: 2356–2361.

  • Thompson AD, Braun BS, Arvand A, Stewart SD, May WA, Chen E, Korenberg J and Denny CT. . 1996 Oncogene 13: 2649–2658.

  • van der Geer P and Pawson T. . 1995 Trend Biomed. Sci. 20: 277–280.

  • van Dijk MA, Voorhoeve P and Murre C. . 1993 Proc. Natl. Acad. Sci. USA 90: 6061–6065.

  • Vogler L, Crist W, Bockman D, Pearl E, Lawton A and Cooper M. . 1978 N. Engl. J. Med. 298: 872–878.

  • Wicks IP, Wilkinson D, Salvaris E and Boyd AW. . 1992 Proc. Natl. Acad. Sci. USA 89: 1611–1615.

Download references

Acknowledgements

Supported by NIH grants CA56876 and 2 PO1 CA 50528. Accession #AF145204.

Author information

Authors and Affiliations

  1. Department of Pathology, University of California, San Diego, California, USA

    Xinyu Fu, Shannon McGrath, Martina Pasillas & Mark P Kamps

  2. Department of Pediatrics, Yamanashi Medical University, 110 Shimokatou, Tamaho, Nakakoma, 409-38, Yamanashi, Japan

    Shinpei Nakazawa

Authors
  1. Xinyu Fu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shannon McGrath
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Martina Pasillas
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Shinpei Nakazawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mark P Kamps
    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

Fu, X., McGrath, S., Pasillas, M. et al. EB-1, a tyrosine kinase signal transduction gene, is transcriptionally activated in the t(1;19) subset of pre-B ALL, which express oncoprotein E2a-Pbx1. Oncogene 18, 4920–4929 (1999). https://doi.org/10.1038/sj.onc.1202874

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1202874

  • Springer Nature Limited

Keywords

This article is cited by

Search

Navigation