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.

  • Review
  • Published:

Philadelphia-positive leukemia: a personal perspective

Oncogene volume 21, pages 8536–8540 (2002)Cite this article

Our involvement in leukemia research started when we joined John Stephenson's Laboratory of Viral Carcinogenesis at the NCI in Frederick, MD in 1981. At the time, the finding that cellular homologs of retrovirally transduced oncogenes existed was novel, and we molecularly cloned the human homologs of v-fes and v-fms (Groffen et al., 1982; Heisterkamp et al., 1983a). Moreover, by using a v-abl probe, we detected many hybridizing bands in total human DNA on a Southern blot, indicating that there were sequences in the human genome that contained significant homology to v-abl, and that c-ABL could be a relatively large gene. Thus, we set about to clone human c-ABL. Molecular cloning was a relatively new technology then. One of us (John) returned to England, where he had worked as a student, to construct a human cosmid library in the laboratory of Richard Flavell at the MRC in London. Cosmid cloning was new and had the distinct advantage that it allowed one to double the size of clonable inserts. We isolated the main body of the ABL exons in the form of three cosmids, which spanned 64 kb and spent many hours constructing a simple restriction enzyme map (Heisterkamp et al., 1983b).

Sequencing was then a time-consuming matter, using either a chemical or a chain-termination method. Sequence analysis established the presence of a phosphotyrosine acceptor site in v-ABL and human c-ABL, revealing that they were very conserved and moreover closely resembled those of v-src, v-yes and v-fes/fps (Groffen et al., 1983).

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

References

  • Bartram CR, de Klein A, Hagemeijer A, van Agthoven T, van Kessel AG, Bootsma D, Grosveld G, Ferguson-Smith MA, Davies T, Stone M, Heisterkamp N, Stephenson JR, Groffen J . 1983 Nature 306: 277–280

  • Ben-Neriah Y, Daley GQ, Mes-Masson AM, Witte ON, Baltimore D . 1986 Science 223: 212–214

  • Canaani E, Gale RP, Steiner-Saltz D . 1984 Lancet I: 593–595

  • Chan LC, Karhi KK, Rayter SI, Heisterkamp N, Eridani S, Powles R, Lawler SD, Groffen J, Foulkes JG, Greaves MF, Wiedemann LM . 1987 Nature 325: 635–637

  • Chissoe SL, Bodenteich A, Wang Y-F, Wang Y-P, Burian D, Clifton SW, Crabtree J, Freeman A, Iyer K, Jian L, Ma Y, McLaury H-J, Pan H-Q, Sarhan OH, Toth S, Wang Z, Zhang G, Heisterkamp N, Groffen J, Roe BA . 1995 Genomics 27: 67–82

  • Collins SJ, Kubonishi I, Miyoshi I, Groudine MT . 1984 Science 225: 72–74

  • Dalla-Favera R, Bregni M, Erikson J, Patterson D, Gallo RC, Croce CM . 1982 Proc. Natl. Acad. Sci. USA 24: 7824–7827

  • de Klein A, van Kessel AG, Grosveld G, Bartram CR, Hagemeijer A, Bootsma JR, Spurr NK, Heisterkamp N, Groffen J, Stephenson JR . 1982 Nature 300: 765–767

  • de Klein A, Hagemeijer A, Bartram CR, Houwen R, Hoefsloot L, Carbonell F, Chan L, Barnett M, Greaves M, Kleihauer E, Heisterkamp N, Groffen J, Grosveld G . 1986 Blood 68: 1369–1375

  • Erikson J, Griffin C, ar-Rushdi A, Valtieri M, Hoxie J, Finan J, Emanuel BS, Rovera G, Nowell PC, Croce CM . 1986 Proc. Natl. Acad. Sci. 83: 1807–1811

  • Freed E, Hunter T . 1992 Mol. Cell. Biol. 12: 1312–1323

  • Feller SM . 2001 Oncogene 20: 6348–6371

  • Gale RP, Canaani E . 1984 Proc. Natl. Acad. Sci. USA 83: 5648–5652

  • Goldman J . 2001 Semin. Hematol. 38: 28–34

  • Groffen J, Heisterkamp N, Grosveld F, Van de Ven W, Stephenson JR . 1982 Science 216: 1136–1138

  • Groffen J, Heisterkamp N, Reynolds Jr FH, Stephenson JR . 1983 Nature 304: 167–169

  • Groffen J, Stephenson JR, Heisterkamp N, de Klein A, Bartram C R, Grosveld G . 1984 Cell 36: 93–99

  • Hariharan IK, Harris AW, Crawford M, Abud H, Webb E, Cory S, Adams JM . 1989 Mol. Cell. Biol. 7: 2798–2805

  • Heisterkamp N, Groffen J, Stephenson JR, Spurr NK, Goodfellow PN, Solomon E, Carritt B, Bodmer WF . 1982 Nature 299: 747–749

  • Heisterkamp N, Groffen J, Stephenson JR . 1983a Virology 126: 248–258

  • Heisterkamp N, Groffen J, Stephenson JR . 1983b J. Mol. Appl. Genet. 2: 57–68

  • Heisterkamp N, Stephenson JR, Groffen J, Hansen P, de Klein A, Bartram CR, Grosveld G . 1983c Nature 306: 239–242

  • Heisterkamp N, Stam K, Groffen J, de Klein A, Grosveld G . 1985 Nature 315: 758–761

  • Heisterkamp N, Knoppel E, Groffen J . 1987 Nucleic Acids Res. 16: 10069–10081

  • Heisterkamp N, Jenster G, ten Hoeve J, Zovich D, Pattengale PK, Groffen J . 1990 Nature 344: 251–254

  • Hemmeryckx B, Reichert A, Watanabe M, Kaartinen V, de Jong R, Pattengale PK, Groffen J, Heisterkamp N . 2002 Oncogene 21: 3225–3231

  • Hermans A, Heisterkamp N, von Lindern M, van Baal S, Meijer D, van der Plas D, Wiedemann L, Groffen J, Bootsma D, Grosveld G . 1987 Cell 51: 33–40

  • Kardinal C, Konkol B, Schulz A, Posern G, Lin H, Adermann K, Eulitz M, Estrov Z, Talpaz M, Arlinghaus RB, Feller SM . 2000 FASEB J. 14: 1529–1538

  • Kloetzer W, Kurzrock R, Smith L, Talpaz M, Spiller M, Gutterman J, Arlinghaus R . 1985 Virology 140: 230–2388

  • Koh EY, Daley GQ . 2001 Chronic myeloid leukemia. Biology and treatment Carella AM, Daley GQ, Eaves CJ, Goldman JM and Hehlmann R (eds) London, UK: Martin Dunitz Ltd pp 55–72

    Google Scholar 

  • Konopka JB, Watanabe SM, Singer JW, Collins SJ, Witte ON . 1985 Proc. Natl. Acad. Sci. USA 82: 1810–1814

  • Mauro MJ, O'Dwyer M, Heinrich MC, Druker BJ . 2002 J. Clin. Oncol. 20: 325–334

  • Mes-Masson A-M, McLaughlin J, Daley GQ, Paskind M, Witte ON . 1986 Proc. Natl. Acad. Sci. 83: 9768–9772

  • Nowell PC, Hungerford DA . 1960 Science 132: 1497

  • Pendergast AM, Gishizky ML, Havlik MH, Witte ON . 1993 Mol. Cell. Biol. 13: 1728–1736

  • Peters DG, Hoover RR, Gerlach MJ, Koh EY, Zhang H, Choe K, Kirschmeier P, Bishop WR, Daley GQ . 2001 Blood 97: 1404–1412

  • Reichert A, Heisterkamp N, Daley GQ, Groffen J . 2001 Blood 97: 1399–1403

  • Rowley JD . 1973 Nature 243: 290–293

  • Shtivelman E, Lifshitz B, Gale RP, Canaani E . 1985 Nature 315: 550–554

  • Stam K, Heisterkamp N, Grosveld G, de Klein A, Verma RS, Coleman M, Dosik H, Groffen J . 1985 N. Engl. J. Med. 313: 1429–1433

  • Stam K, Heisterkamp N, Reynolds Jr FH, Groffen J . 1987 Mol. Cell. Biol. 7: 1955–1960

  • Tari AM, Arlinghaus R, Berestein-Lopez G . 1997 Biochem. Biophys. Res. Comm. 235: 383–388

  • Taub R, Kirsch I, Morton C, Lenoir G, Swan D, Tronick S, Aaronson S, Leder P . 1982 Proc. Natl. Acad. Sci. USA 24: 7837–7841

Download references

Acknowledgements

This work was supported by PHS grant CA90321 and CA50248 (NH), by the T.J. Martell Foundation (N Heisterkamp and J Groffen) and by the Kenneth T and Eileen L Norris Foundation for Leukemia Research (J Groffen).

Author information

Authors and Affiliations

  1. Division of Hematology/Oncology, Ms#54, Section of Molecular Carcinogenesis, Childrens Hospital Los Angeles Research Institute, 4650 Sunset Boulevard, Los Angeles, 90027, California, CA, USA

    Nora Heisterkamp & John Groffen

  2. Keck School of Medicine of the University of Southern California, Los Angeles, 90027, California, CA, USA

    Nora Heisterkamp & John Groffen

Authors
  1. Nora Heisterkamp
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. John Groffen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nora Heisterkamp.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Heisterkamp, N., Groffen, J. Philadelphia-positive leukemia: a personal perspective. Oncogene 21, 8536–8540 (2002). https://doi.org/10.1038/sj.onc.1206080

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1206080

Keywords

This article is cited by

Search

Advanced search

Quick links