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:

Translocations involving anaplastic lymphoma kinase (ALK)

Abstract

Anaplastic large-cell lymphoma (ALCL) comprises a group of non-Hodgkin's lymphomas (NHLs) that were first described in 1985 by Stein and co-workers and are characterized by the expression of the CD30/Ki-1 antigen (Stein et al., 1985). Approximately half of these lymphomas are associated with a typical chromosomal translocation, t(2;5)(p23;q35). Much confusion about the exact classification and clinicopathological features of this subgroup of NHL was clarified with the identification of NPM–ALK (nucleophosmin-anaplastic lymphoma kinase) as the oncogene created by the t(2;5) (Morris et al., 1994). With the discovery of NPM–ALK as the specific lymphoma gene mutation, this NHL subtype could be redefined on the molecular level. This achievement was enhanced by the availability of specific antibodies that recognize ALK fusion proteins in paraffin-embedded lymphoma tissues. Several excellent recent reviews have summarized the histopathological and molecular findings of ALCL and their use in the classification of this lymphoma entity (Anagnostopoulos and Stein, 2000; Benharroch et al., 1998; Drexler et al., 2000; Foss et al., 2000; Gogusev and Nezelof, 1998; Kadin and Morris, 1998; Ladanyi, 1997; Morris et al., 2001; Shiota and Mori, 1996; Skinnider et al., 1999; Stein et al., 2000). This review will focus on the molecular function and signal transduction pathways activated by ALK fusion oncogenes, with recent advances and possible clinical implications to be discussed.

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

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

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

Figure 1
Figure 2
Figure 5
Figure 3
Figure 4

Similar content being viewed by others

References

  • Anagnostopoulos I, Stein H . 2000 Pathology 21: 178–189

  • Bai RY, Coutinho S, Morris SW, Peschel C, Duyster J . 1998a Blood 92: 2110a

  • Bai RY, Dieter P, Peschel C, Morris SW, Duyster J . 1998b Mol. Cell. Biol. 18: 6951–6961

  • Bai RY, Ouyang T, Miething C, Morris SW, Peschel C, Duyster J . 2000 Blood 96: 4319–4327

  • Barbacid M . 1995 Ann. NY Acad. Sci. 766: 442–458

  • Beg AA, Baltimore D . 1996 Science 274: 782–784

  • Benharroch D, Meguerian-Bedoyan Z, Lamant L, Amin C, Brugieres L, Terrier-Lacombe MJ, Haralambieva E, Pulford K, Pileri S, Morris SW, Mason DY, Delsol G . 1998 Blood 91: 2076–2084

  • Beylot-Barry M, Groppi A, Vergier B, Pulford K, Merlio JP . 1998 Blood 91: 4668–4676

  • Bischof D, Pulford K, Mason DY, Morris SW . 1997 Mol. Cell. Biol. 17: 2312–2325

  • Borer RA, Lehner CF, Eppenberger HM, Nigg EA . 1989 Cell 56: 379–390

  • Brunel V, Sainty D, Carbuccia N, Arnoulet C, Costello R, Mozziconacci MJ, Simonetti J, Coignet L, Gabert J, Stoppa AM, Birg F, Lafagepochitaloff M . 1995 Genes Chrom. Cancer 14: 307–312

  • Butti MG, Bongarzone I, Ferraresi G, Mondellini P, Borrello MG, Pierotti MA . 1995 Genomics 28: 15–24

  • Cantley LC, Auger KR, Carpenter C, Duckworth B, Graziani A, Kapeller R, Soltoff S . 1991 Cell 64: 281–302

  • Chan PK, Chan FY . 1995 Biochim. Biophys. Acta 1262: 37–42

  • Chan PK Chan FY, Morris SW, Xie Z . 1997 Nucleic Acids Res. 25: 1225–1232

  • Chan PK, Liu QR, Durban E . 1990 Biochem. J. 270: 549–552

  • Chan WY, Liu QR, Borjigin J, Busch H, Rennert OM, Tease LA, Chan PK . 1989 Biochemistry 28: 1033–1039

  • Chauhan AK, Li YS, Deuel TF . 1993 Proc. Natl. Acad. Sci. USA 90: 679–682

  • Choudhuri R, Zhang HT, Donnini S, Ziche M, Bicknell R . 1997 Cancer Res. 57: 1814–1819

  • Colleoni GW, Bridge JA, Garicochea B, Liu J, Filippa DA, Ladanyi M . 2000 Am. J. Pathol. 156: 781–789

  • Cordell JL, Pulford KA, Bigerna B, Roncador G, Banham A, Colombo E, Pelicci PG, Mason DY, Falini B . 1999 Blood 93: 632–642

  • Courty J, Dauchel MC, Caruelle D, Perderiset M, Barritault D . 1991 Biochem. Biophys. Res. Commun. 180: 145–151

  • Czubayko F, Riegel AT, Wellstein A . 1994 J. Biol. Chem. 269: 21358–21363

  • Czubayko F, Schulte AM, Berchem GJ, Wellstein A . 1996 Proc. Natl. Acad. Sci. USA 93: 14753–14758

  • Delsol G, Lamant L, Mariame B, Pulford K, Dastugue N, Brousset P, Rigal-Huguet F, al Saati T, Cerretti DP, Morris SW, Mason DY . 1997 Blood 89: 1483–1490

  • Drexler HG, Gignac SM, von Wasielewski R, Werner M, Dirks WG . 2000 Leukemia 14: 1533–1559

  • Durkop H, Latza U, Hummel M, Eitelbach F, Seed B, Stein H . 1992 Cell 68: 421–427

  • Ellis TM, Simms PE, Slivnick DJ, Jack HM, Fisher RI . 1993 J. Immunol. 151: 2380–2389

  • Falini B, Bigerna B, Fizzotti M, Pulford K, Pileri SA, Delsol G, Carbone A, Paulli M, Magrini U, Menestrina F, Giardini R, Pilotti S, Mezzelani A, Ugolini B, Billi M, Pucciarini A, Pacini R, Pelicci PG, Flenghi L . 1998 Am. J. Pathol. 153: 875–886

  • Falini B, Pileri S, Zinzani PL, Carbone A, Zagonel V, Wolf-Peeters C, Verhoef G, Menestrina F, Todeschini G, Paulli M, Lazzarino M, Giardini R, Aiello A, Foss HD, Araujo I, Fizzotti M, Pelicci PG, Flenghi L, Martelli MF, Santucci A . 1999a Blood 93: 2697–2706

  • Falini B, Pulford K, Pucciarini A, Carbone A, De Wolf-Peeters C, Cordell J, Fizzotti M, Santucci A, Pelicci PG, Pileri S, Campo E, Ott G, Delsol G, Mason DY . 1999b Blood 94: 3509–3515

  • Fang W, Hartmann N, Chow DT, Riegel AT, Wellstein A . 1992 J. Biol. Chem. 267: 25889–25897

  • Foss HD, Marafioti T, Stein H . 2000 Pathologe 21: 124–136

  • Fujimoto J, Shiota M, Iwahara T, Seki N, Satoh H, Mori S, Yamamoto T . 1996 Proc. Natl. Acad. Sci. USA 93: 4181–4186

  • Gascoyne RD, Aoun P, Wu D, Chhanabhai M, Skinnider BF, Greiner TC, Morris SW, Connors JM, Vose JM, Viswanatha DS, Coldman A, Weisenburger DD . 1999 Blood 93: 3913–3921

  • Gogusev J, Nezelof C . 1998 Hematol. Oncol. Clin. North. Am. 12: 445–463

  • Greco A, Mariani C, Miranda C, Lupas A, Pagliardini S, Pomati M, Pierotti MA . 1995 Mol. Cell. Biol. 15: 6118–6127

  • Griffin CA, Hawkins AL, Dvorak C, Henkle C, Ellingham T, Perlman EJ . 1999 Cancer Res. 59: 2776–2780

  • Harris NL, Jaffe ES, Stein H, Banks PM, Chan JK, Cleary ML, Delsol G, De Wolf-Peeters C, Falini B, Gatter KC . 1994 Blood 84: 1361–1392

  • Hernandez L, Pinyol M, Hernandez S, Bea S, Pulford K, Rosenwald A, Lamant L, Falini B, Ott G, Mason DY, Delsol G, Campo E . 1999 Blood 94: 3265–3268

  • Hsu H, Shu HB, Pan MG, Goeddel DV . 1996 Cell 84: 299–308

  • Hübinger G, Scheffrahn I, Muller E, Bai R, Duyster J, Morris SW, Schrezenmeier H, Bergmann L . 1999a Exp. Hematol. 27: 1796–1805

  • Hübinger G, Wehnis E, Maurer U, Morris SW, Bergmann L . 1999b Blood 94: 598a

  • Iwahara T, Fujimoto J, Wen D, Cupples R, Bucay N, Arakawa T, Mori S, Ratzkin B, Yamamoto T . 1997 Oncogene 14: 439–449

  • Jiang YP, Wang H, D'Eustachio P, Musacchio JM, Schlessinger J, Sap J . 1993 Mol. Cell. Biol. 13: 2942–2951

  • Kadin ME . 1997 Cancer Surv. 30: 77–86

  • Kadin ME, Morris SW . 1998 Leuk. Lymphoma 29: 249–256

  • Khwaja A . 1999 Nature 401: 33–34

  • Kinney MC, Kadin ME . 1999 Am. J. Clin. Pathol. 111: S56–S67

  • Kinney MC, Greer JP, Kadin ME, DeCouteau JF, Collins RD . 1996 Lab. Invest. 74: 114A

  • Kuefer MU, Look AT, Pulford K, Behm FG, Pattengale PK, Mason DY, Morris SW . 1997 Blood 90: 2901–2910

  • Ladanyi M . 1997 Cancer Surv. 30: 59–75

  • Ladanyi M, Cavalchire G . 1996a Diagn. Mol. Pathol. 5: 154–158

  • Ladanyi M, Cavalchire G . 1996b Genes Chromos. Cancer 15: 173–177

  • Lamant L, Dastugue N, Pulford K, Delsol G, Mariame B . 1999 Blood 93: 3088–3095

  • Lamant L, Pulford K, Bischof D, Morris SW, Mason DY, Delsol G, Mariame B . 2000 Am. J. Pathol. 156: 1711–1721

  • Lawrence B, Perez-Atayde A, Hibbard MK, Rubin BP, Dal Cin P, Pinkus JL, Pinkus GS, Xiao S, Yi ES, Fletcher CD, Fletcher JA . 2000 Am. J. Pathol. 157: 377–384

  • Lee SY, Park CG, Choi Y . 1996 J. Exp. Med. 183: 669–674

  • Leevers SJ, Vanhaesebroeck B, Waterfield MD . 1999 Curr. Opin. Cell. Biol. 11: 219–225

  • Li S, Gillessen S, Tomasson MH, Dranoff G, Gilliland DG, van Etten RA . 2001 Blood 97: 1442–1450

  • Li YS, Milner PG, Chauhan AK, Watson MA, Hoffman RM, Kodner CM, Milbrandt J, Deuel TF . 1990 Science 250: 1690–1694

  • Liu QR, Chan PK . 1991 Eur. J. Biochem. 200: 715–721

  • Liu ZG, Hsu H, Goeddel DV, Karin M . 1996 Cell 87: 565–576

  • Luthra R, Pugh WC, Waasdorp M, Morris W, Cabanillas F, Chan PK, Sarris AH . 1998 Hematopathol. Mol. Hematol. 11: 173–183

  • Ma Z, Cools J, Marynen P, Cui X, Siebert R, Gesk S, Schlegelberger B, Peeters B, De Wolf-Peeters C, Wlodarska I, Morris SW . 2000 Blood 95: 2144–2149

  • Maeda N, Nishiwaki T, Shintani T, Hamanaka H, Noda A . 1996 J. Biol. Chem. 271: 21446–21452

  • Mahajan R, Delphin C, Guan T, Gerace L, Melchior F . 1997 Cell 88: 97–107

  • Mason DY, Pulford KA, Bischof D, Kuefer MU, Butler LH, Lamant L, Delsol G, Morris SW . 1998 Cancer Res. 58: 1057–1062

  • Michaud N, Goldfarb DS . 1991 J. Cell. Biol. 112: 215–223

  • Miething C, Bai R, Morris SW, von Schilling C, Schmidt B, Peschel C, Duyster J . 2000 Blood 96: 93a

  • Mir SS, Richter BW, Duckett CS . 2000 Blood 96: 4307–4312

  • Mitev L, Christova S, Hadjiev E, Guenova M, Oucheva R, Valkov I, Manolova Y . 1998 Leuk. Lymphoma 28: 613–616

  • Morris SW, Kirstein MN, Valentine MB, Dittmer KG, Shapiro DN, Saltman DL, Look AT . 1994 Science 263: 1281–1284

  • Morris SW, Naeve C, Mathew P, James PL, Kirstein MN, Cui X, Witte DP . 1997 Oncogene 14: 2175–2188

  • Morris SW, Xue L, Ma Z, Kinney MC . 2001 Br. J. Haematol. 113: 275–279

  • Nakamura S, Shiota M, Nakagawa A, Yatabe Y, Kojima M, Motoori T, Suzuki R, Kagami Y, Ogura M, Morishima Y, Mizoguchi Y, Okamoto M, Seto M, Koshikawa T, Mori S, Suchi T . 1997 Am. J. Surg. Pathol. 21: 1420–1432

  • Neckameyer WS, Shibuya M, Hsu MT, Wang LH . 1986 Mol. Cell. Biol. 6: 1478–1486

  • Nieborowska-Skorska M, Slupianek A, Zhang Q, Raghunath PN, Xue L, Morris SW, Wasik M, Skorski T . 2000 Blood 96: 2017a

  • Ochs R, Lischwe M, O'Leary P, Busch H . 1983 Exp. Cell. Res. 146: 139–149

  • Okuda M, Horn HF, Tarapore P, Tokuyama Y, Smulian AG, Chan PK, Knudsen ES, Hofmann IA, Snyder JD, Bove KE, Sukasawa K . 2000 Cell 103: 127–140

  • Park JP, Curran MJ, Levy NB, Davis TH, Elliott JH, Mohandas TK . 1997 Cancer Genet. Cytogenet. 96: 118–122

  • Pawson T, Gish D . 1992 Cell 71: 359–362

  • Peter M, Nakagawa J, Doree M, Labbe JC, Nigg EA . 1990 Cell 60: 791–801

  • Pfeifer W, Levi E, Petrogiannis-Haliotis T, Lehmann L, Wang Z, Kadin ME . 1999 Am. J. Pathol. 155: 1353–1359

  • Pileri SA, Pulford K, Mori S, Mason DY, Sabattini E, Roncador G, Piccioli M, Ceccarelli C, Piccaluga PP, Santini D, Leone O, Stein H, Falini B . 1997 Am. J. Pathol. 150: 1207–1211

  • Pulford K, Falini B, Banham AH, Codrington D, Roberton H, Hatton C, Mason DY . 2000 Blood 96: 1605–1607

  • Pulford K, Falini B, Cordell J, Rosenwald A, Ott G, Muller-Hermelink HK, MacLennan KA, Lamant L, Carbone A, Campo E, Mason DY . 1999 Am. J. Pathol. 154: 1657–1663

  • Pulford K, Lamant L, Morris SW, Butler LH, Wood KM, Stroud D, Delsol G, Mason DY . 1997 Blood 89: 1394–1404

  • Raulo E, Chernousov MA, Carey DJ, Nolo R, Rauvala H . 1994 J. Biol. Chem. 269: 12999–13004

  • Redner RL, Rush EA, Faas S, Rudert WA, Corey SJ . 1996 Blood 87: 882–886

  • Rodrigues GA, Park M . 1993 Mol. Cell. Biol. 13: 6711–6722

  • Rosenwald A, Ott G, Pulford K, Katzenberger T, Kuhl J, Kalla J, Ott MM, Mason DY, Muller-Hermelink HK . 1999 Blood 94: 362–364

  • Sandlund JT, Pui CH, Roberts WM, Santana VM, Morris SW, Berard CW, Hutchison RE, Ribeiro RC, Mahmoud H, Crist WM . 1994a Blood 84: 2467–2471

  • Sandlund JT, Pui CH, Santana VM, Mahmoud H, Roberts WM, Morris S, Raimondi S, Ribeiro R, Crist WM, Lin JS . 1994b J. Clin. Oncol. 12: 895–898

  • Schulte AM, Lai S, Kurtz A, Czubayko F, Riegel AT, Wellstein A . 1996 Proc. Natl. Acad. Sci. USA 93: 14759–14764

  • Schulte AM, Wellstein A . 1997 Tumor Angiogenesis Bicknell R, Lewis CM and Ferrara N. (eds). Oxford University Press: Oxford, New York, Tokyo pp. 273–289

    Google Scholar 

  • Schwab U, Stein H, Gerdes J, Lemke H, Kirchner H, Schaadt M, Diehl V . 1982 Nature 299: 65–67

  • Sexl V, Piekorz R, Moriggl R, Rohrer J, Brown MP, Bunting KD, Rothammer K, Roussel MF, Ihle JN . 2000 Blood 96: 2277–2283

  • Shiota M, Mori S . 1996 Leuk. Lymphoma 23: 25–32

  • Shiota M, Fujimoto J, Semba T, Satoh H, Yamamoto T, Mori S . 1994a Oncogene 9: 1567–1574

  • Shiota M, Fujimoto J, Takenaga M, Satoh H, Ichinohasama R, Abe M, Nakano M, Yamamoto T, Mori S . 1994b Blood 84: 3648–3652

  • Shiota M, Nakamura S, Ichinohasama R, Abe M, Akagi T, Takeshita M, Mori N, Fujimoto J, Miyauchi J, Mikata A, Nanba K, Takami T, Yamabe H, Takano Y, Izumo T, Nagatani T, Mohri N, Nasu K, Satoh H, Katano H, Fujimoto J, Yamamoto T, Mori S . 1995 Blood 86: 1954–1960

  • Skinnider BF, Connors JM, Sutcliffe SB, Gascoyne RD . 1999 Hematol. Oncol. 17: 137–148

  • Slupianek A, Nieborowska-Skorska M, Hoser G, Morrione A, Majewski M, Xue L, Morris SW, Wasik MA, Skorski T . 2001 Cancer Res. 61: 2194–2199

  • Smith CA, Gruss HJ, Davis T, Anderson D, Farrah T, Baker E, Sutherland GR, Brannan CI, Copeland NG, Jenkins NA . 1993 Cell 73: 1349–1360

  • Souttou B, Juhl H, Hackenbruck J, Rockseisen M, Klomp HJ, Raulais D, Vigny M, Wellstein A . 1998 J. Natl. Cancer Inst. 90: 1468–1473

  • Stein H, Foss HD, Durkop H, Marafioti T, Delsol G, Pulford K, Pileri S, Falini B . 2000 Blood 96: 3681–3695

  • Stein H, Mason DY, Gerdes J, O'Connor N, Wainscoat J, Pallesen G, Gatter K, Falini B, Delsol G, Lemke H, Schwarting R, Lennert K . 1985 Blood 66: 848–858

  • Stoica GE, Kuo A, Aigner A, Sunitha I, Souttou B, Malercyk C, Caughey DJ, Went D, Karavanov A, Riegel AT, Wellstein A . 2001 J. Biol. Chem. 18: 16772–16779

  • Szebeni A, Herrera JE, Olson MO . 1995 Biochemistry 34: 8037–8042

  • Tian ZG, Longo DL, Funakoshi S, Asai O, Ferris DK, Widmer M, Murphy WJ . 1995 Cancer Res. 55: 5335–5341

  • Touriol C, Greenland C, Lamant L, Pulford K, Bernard F, Rousset T, Mason DY, Delsol G . 2000 Blood 95: 3204–3207

  • Trinei M, Lanfrancone L, Campo E, Pulford K, Mason DY, Pelicci PG, Falini B . 2000 Cancer Res. 60: 793–798

  • Trumper L, Pfreundschuh M, Bonin FV, Daus H . 1998 Br. J. Haematol. 103: 1138–1144

  • Ueno H, Honda H, Nakamoto T, Yamagata T, Sasaki K, Miyagawa K, Mitani K, Yazaki Y, Hirai H . 1997 Oncogene 14: 3067–3072

  • Ueno H, Sasaki K, Kozutsumi H, Miyagawa K, Mitani K, Yazaki Y, Hirai H . 1996 J. Biol. Chem. 271: 27707–27714

  • Valdez BC, Perlaky L, Henning D, Saijo Y, Chan PK, Busch H . 1994 J. Biol. Chem. 269: 23776–23783

  • Van Antwerp DJ, Martin SJ, Kafri T, Green DR, Verma IM . 1996 Science 274: 787–789

  • Wellstein A, Fang WJ, Khatri A, Lu Y, Swain SS, Dickson RB, Sasse J, Riegel AT, Lippman ME . 1992 J. Biol. Chem. 267: 2582–2587

  • Yoneda-Kato N, Look AT, Kirstein MN, Valentine MB, Raimondi SC, Cohen KJ, Carroll AJ, Morris SW . 1996 Oncogene 12: 265–275

  • Yung BY, Busch H, Chan PK . 1985 Biochim. Biophys. Acta 826: 167–173

  • Zatsepina OV, Rousselet A, Chan PK, Olson MO, Jordan EG, Bornens M . 1999 J. Cell. Sci. 112: 455–466

Download references

Acknowledgements

This work was supported by a grant from the Wilhelm-Sander Stiftung and Mildred-Scheel Stiftung to J Duyster, by SFB grant No 456 to J Duyster, by National Cancer Institute (NCI) grants CA69129 and CA76301, and CORE grant CA21765 to SW Morris, and by the American-Lebanese Syrian Associated Charities (ALSAC), St Jude Children's Research Hospital.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Justus Duyster or Stephan W Morris.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Duyster, J., Bai, RY. & Morris, S. Translocations involving anaplastic lymphoma kinase (ALK). Oncogene 20, 5623–5637 (2001). https://doi.org/10.1038/sj.onc.1204594

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1204594

Keywords

This article is cited by

Search

Quick links