Journal Mobile Options
Table of Contents
Vol. 107, No. 2, 2002
Issue release date: March 2002
Acta Haematol 2002;107:101–107

The 8p11 Myeloproliferative Syndrome: A Distinct Clinical Entity Caused by Constitutive Activation of FGFR1

Macdonald D. · Reiter A. · Cross N.C.P.
aDepartment of Haematology, Faculty of Medicine, Imperial College of Science, Technology and Medicine, Charing Cross Hospital, London, UK; bIII Medizinische Universitätsklinik, Klinikum Mannheim, Germany; cWessex Regional Genetics Laboratory, Salisbury, dHuman Genetics Division, University of Southampton School of Medicine, Southampton, UK

Individual Users: Register with Karger Login Information

Please create your User ID & Password

Contact Information

I have read the Karger Terms and Conditions and agree.

To view the fulltext, please log in

To view the pdf, please log in


Several recurrent translocations that involve chromosome band 8p11 have been described in myeloid malignancies. These translocations target two distinct genes: (1) FGFR1, a receptor tyrosine kinase for fibroblast growth factors, and (2) MOZ, a putative histone acetyltransferase whose precise function remains to be defined. Disruption of FGFR1 is associated with a disease entity known as the 8p11 myeloproliferative syndrome (EMS)/stem cell leukemia-lymphoma syndrome, a chronic myeloproliferative disorder that frequently presents with eosinophilia and associated T-cell lymphoblastic lymphoma. The disease is aggressive and rapidly transforms to acute leukaemia, usually of myeloid phenotype. Currently, only allogeneic stem cell transplantation appears to be effective in eradicating or suppressing the malignant clone. To date, four gene fusions associated with distinct translocations have been described in EMS: the t(8;13)(p11;q12), t(8;9)(p11;q33), t(6;8)(q27;p11) and t(8;22)(p11q22) fuse ZNF198, CEP110, FOP and BCR, respectively, to FGFR1. The resulting fusion proteins have constitutive tyrosine kinase activity and activate multiple signal transduction pathways. These pathways and the fusion proteins are attractive targets for targeted signal transduction therapy.

Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.


  1. Shepherd PCA, Ganesan TS, Galton DA: Haematological classification of the chronic myeloid leukaemias. Baillières Clin Haematol 1987;1:887–906.

    External Resources

  2. Oscier D: Atypical chronic myeloid leukemias. Pathol Biol 1997;45:587–593.
  3. Bain BJ: The relationship between the myelodysplastic syndromes and the myeloproliferative disorders. Leuk Lymphoma 1999;34:443–449.
  4. Macdonald D, Aguiar RCT, Mason PJ, Goldman JM, Cross NCP: A new myeloproliferative disorder associated with chromosomal translocations involving 8p11: A review. Leukemia 1995;9:1628–1630.

    External Resources

  5. Inhorn RC, Aster JC, Roach SA, Slapak CA, Soiffer R, Tantravahi R, Stone RM: A syndrome of lymphoblastic lymphoma, eosinophilia, and myeloid hyperplasia/malignancy associated with t(8;13)(p11;q11): Description of a distinctive clinicopathologic entity. Blood 1195;85:1881–1887.
  6. Friedhoff F, Rajendra B, Moody R, Alapatt T: Novel reciprocal translocation between chromosomes 8 and 9 found in a patient with myeloproliferative disorder. Cancer Genet Cytogenet 1983;9:391–394.
  7. Lewis JP, Jenks H, Lazerson J: Philadelphia chromosome-negative chronic myelogenous leukemia in a child with t(8;9)(p11 or 12;q34). Am J Pediatr Hematol Oncol 1983;5:265–269.
  8. Vannier JP, Bizet M, Bastard C, Bernard A, Ducastelle T, Tron P: Simultaneous occurrence of a T-cell lymphoma and a chronic myelogenous leukemia with an unusual karyotype. Leuk Res 1984;8:647–657.
  9. Abruzzo LV, Jaffe ES, Cotelingam JD, Whang-Peng J, Del DV, Jr, Medeiros LJ: T-cell lymphoblastic lymphoma with eosinophilia associated with subsequent myeloid malignancy. Am J Surg Pathol 1992;16:236–245.
  10. Jotterand BM, Muhlematter D, Wicht M, Delacretaz F, Schmidt PM: t(8;9)(p11;q32) in atypical chronic myeloid leukaemia: A new cytogenetic-clinicopathologic association? Br J Haematol 1992;81:307–308.
  11. Rao PH, Cesarman G, Coleman M, Acaron S, Verma RS: Cytogenetic evidence for extramedullary blast crisis with t(8;13)(q11;p11) in chronic myelomonocytic leukemia. Acta Haematol 1992;88:201–203.
  12. Fagan K, Hyde S, Harrison P: Translocation (8;13) and T-cell lymphoma. A case report. Cancer Genet Cytogenet 1993;65:71–73.
  13. Oscier DG, Gardiner A, Dyer M: t(8;9) in chronic myeloid leukaemia. Br J Haematol 1993;83:176–177.
  14. Leslie J, Barker T, Glancy M, Jennings B, Pearson J: t(8;13) (p11;q12) translocation in a myeloproliferative disorder associated with a T-cell non-Hodgkin lymphoma. Br J Haematol 1994;86:876–878.
  15. Macdonald D, Sheerin SM, Cross NCP, Spencer A, Goldman JM: An atypical myeloproliferative disorder with a t(8;13)(p11;q12): A third case. Br J Haematol 1994;86:879–880.
  16. Elsner S, Martin H, Rode C, Wassmann B, Ganser A, Hoelzer D: An uncommon translocation t(6;8) associated with atypical acute myeloid leukaemia/myeloproliferative disease detected by fluorescence in-situ hybridization. Br J Haematol 1994;87:124.
  17. Behringer D, Schaefer HE, Kunzmann R, Mertelsmann R, Dolken G: Translocation t(8;13) in a patient with T cell lymphoma and features of a myeloproliferative syndrome. Leukemia 1995;9:988–992.

    External Resources

  18. Michaux L, Mecucci C, Pereira Velloso ER, Dierlamm J, Criel A, Louwagie A, van Orshoven A, Van den BH: About the t(8;13) (p11;q12) clinico-pathologic entity. Blood 1996;87:1658–1659.
  19. Nakayama H, Inamitsu T, Ohga S, Kai T, Suda T, Suda M, Matsuzaki A, Ueda K: Chronic myelomonocytic leukaemia with t(8;9) (p11;q34) in childhood: An example of the 8p11 myeloproliferative disorder? Br J Haematol 1996;92:692–695.
  20. van den Berg H, Kroes W, van der Schoot CE, Dee R, Pals ST, Bouts TH, Slater RM: A young child with acquired t(8;9)(p11;q34): Additional proof that 8p11 is involved in mixed myeloid/T lymphoid malignancies. Leukemia 1996;10:1252–1253.
  21. Aguiar RCT, Chase A, Coulthard S, Macdonald DH, Carapeti M, Reiter A, Sohal J, Lennard A, Goldman JM, Cross NCP: Abnormalities of chromosome band 8p11 in leukemia: Two clinical syndromes can be distinguished on the basis of MOZ involvement. Blood 1997;90:3130–3135.
  22. Somers GR, Slater H, Rockman S, Ekert H, Southey MC, Chow CW, Armes JE, Venter DJ: Coexistent T-cell lymphoblastic lymphoma and an atypical myeloproliferative disorder associated with t(8;13)(p21;q14). Pediatr Pathol Lab Med 1997;17:141–158.
  23. Still IH, Chernova O, Hurd D, Stone RM, Cowell JK: Molecular characterization of the t(8;13)(p11;q12) translocation associated with an atypical myeloproliferative disorder: Evidence for three discrete loci involved in myeloid leukemias on 8p11. Blood 1997;90:3136–3141.
  24. Chaffanet M, Popovici C, Leroux D, Jacrot M, Adelaide J, Dastugue N, Gregoire MJ, Hagemeijer A, Lafage-Pochitaloff M, Birnbaum D, Pebusque MJ: t(6;8), t(8;9) and t(8;13) translocations associated with stem cell myeloproliferative disorders have close or identical breakpoints in chromosome region 8p11-12. Oncogene 1998;16:945–949.

    External Resources

  25. Chernova O, Still I, Kalaycio M, Hoeltge G, Cowell JK: Characterization of the breakpoints in a t(8;13)(p11;q12) translocation from a patient with myeloproliferative disease using fluorescence in situ hybridization. Genes Chromosomes Cancer 1998;21:160–165.
  26. Martinez-Climent JA, Vizcarra E, Benet I, Marugan I, Terol MJ, Solano C, Arbona C, Tormo M, Comes AM, Garcia-Conde J: Cytogenetic response induced by interferon alpha in the myeloproliferative disorder with eosinophilia, T cell lymphoma and the chromosomal translocation t(8;13)(p11;q12). Leukemia 1998;12:999–1000.
  27. Matsumoto K, Morita K, Takada S, Sakura T, Shiozaki H, Murakami H, Miyawaki S: A chronic myelogenous leukemia-like myeloproliferative disorder accompanied by T-cell lymphoblastic lymphoma with chromosome translocation t(8;13)(p11;q12): A Japanese case. Int J Hematol 1999;70:278–282.
  28. Popovici C, Zhang B, Gregoire MJ, Jonveaux P, Lafage-Pochitaloff M, Birnbaum D, Pebusque MJ: The t(6;8)(q27;p11) translocation in a stem cell myeloproliferative disorder fuses a novel gene, FOP, to fibroblast growth factor receptor 1. Blood 1999;93:1381–1389.
  29. Guasch G, Mack GJ, Popovici C, Dastugue N, Birnbaum D, Rattner JB, Pebusque MJ: FGFR1 is fused to the centrosome-associated protein CEP110 in the 8p12 stem cell myeloproliferative disorder with t(8;9)(p12;q33). Blood 2000;95:1788–1796.
  30. Demiroglu A, Steer EJ, Heath C, Taylor K, Bentley M, Allen SL, Koduru P, Brody JP, Hawson G, Rodwell R, Doody M-L, Carnicero F, Reiter A, Goldman JM, Melo JV, Cross NCP: The t(8;22) in chronic myeloid leukemia fuses BCR to FGFR1: Transforming activity and specific inhibition of FGFR1 fusion proteins. Blood 2001;98:3778–3783.
  31. Mugneret F, Chaffanet M, Maynadie M, Guasch G, Favre B, Casasnovas O, Birnbaum D, Pebusque MJ: The 8p12 myeloproliferative disorder. t(8;19)(p12;q13.3): A novel translocation involving the FGFR1 gene. Br J Haematol 2000;111:647–649.

    External Resources

  32. Sohal J, Chase A, Mould S, Corcoran M, Oscier D, Iqbal S, Parker S, Welborn J, Harris I, Martinelli G, Montefusco V, Sinclair P, Wilkins BS, van den Berg H, Vanstraelen D, Goldman JM, Cross NCP: Identification of four new translocations involving FGFR1 in myeloid disorders. Genes Chromosomes Cancer 2001;32:155–163.
  33. Popovici C, Adelaide J, Ollendorff V, Chaffanet M, Guasch G, Jacrot M, Leroux D, Birnbaum D, Pebusque MJ: Fibroblast growth factor receptor 1 is fused to FIM in stem-cell myeloproliferative disorder with t(8;13). Proc Natl Acad Sci USA 1998;95:5712–5717.
  34. Reiter A, Sohal J, Kulkarni S, et al: Consistent fusion of ZNF198 to the fibroblast growth factor receptor-1 in the t(8;13)(p11;q12) myeloproliferative syndrome. Blood 1998;92:1735–1742.
  35. Smedley D, Hamoudi R, Clark J, Warren W, Abdul-Rauf M, Somers G, Venter D, Fagan K, Cooper C, Shipley J: The t(8;13)(p11;q11–12) rearrangement associated with an atypical myeloproliferative disorder fuses the fibroblast growth factor receptor 1 gene to a novel gene RAMP. Hum Mol Genet 1998;7:637–642.

    External Resources

  36. Xiao S, Nalabolu SR, Aster JC, et al: FGFR1 is fused with a novel zinc-finger gene, ZNF198, in the t(8;13) leukaemia/lymphoma syndrome. Nat Genet 1998;18:84–87.

    External Resources

  37. Ollendorff V, Guasch G, Isnardon D, Galindo R, Birnbaum D, Pebusque MJ: Characterization of FIM-FGFR1, the fusion product of the myeloproliferative disorder-associated t(8;13) translocation. J Biol Chem 1999;274:26922–26930.
  38. Smedley D, Somers G, Venter D, Chow CW, Cooper C, Shipley J: Characterization of a t(8;13)(p11;q11–12) in an atypical myeloproliferative disorder. Genes Chromosomes Cancer 1998;21:70–73.
  39. Kempski H, Macdonald D, Michalski AJ, Roberts T, Goldman JM, Cross NCP, Cowell JK: Localization of the 8;13 translocation breakpoint associated with myeloproliferative disease to a 1.5 Mbp region of chromosome 13. Genes Chromosomes Cancer 1995;12:283–287.
  40. Jiang G, Hunter T: Receptor signaling: When dimerization is not enough. Curr Biol 1999;9:R568–R571.
  41. Mason IJ: The ins and outs of fibroblast growth factors. Cell 1994;78:547–552.
  42. Smedley D, Demiroglu A, Abdul-Rauf M, Heath C, Cooper C, Shipley J, Cross NCP: ZNF198-FGFR1 transforms Ba/F3 cells to growth factor independence and results in high level tyrosine phosphorylation of STATs 1 and 5. Neoplasia 1999;1:349–355.

    External Resources

  43. McWhirter JR, Galasso DL, Wang JY: A coiled-coil oligomerization domain of Bcr is essential for the transforming function of Bcr-Abl oncoproteins. Mol Cell Biol 1993;13, 7587–7595.
  44. Carroll M, Tomasson MH, Barker GF, Golub TR, Gilliland DG: The TEL/platelet-derived growth factor beta receptor (PDGF beta R) fusion in chronic myelomonocytic leukemia is a transforming protein that self-associates and activates PDGF beta R kinase-dependent signaling pathways. Proc Natl Acad Sci USA 1996;93:14845–14850.
  45. Xiao S, McCarthy JG, Aster JC, Fletcher JA: ZNF198-FGFR1 transforming activity depends on a novel proline-rich ZNF198 oligomerization domain. Blood 2000;96:699–704.
  46. Druker BJ, Sawyers CL, Kantarjian H, Resta DJ, Reese SF, Ford JM, Capdeville R, Talpaz M: Activity of a specific inhibitor of the BCR-ABL tyrosine kinase in the blast crisis of chronic myeloid leukemia and acute lymphoblastic leukemia with the Philadelphia chromosome. N Engl J Med 2001;344:1038–1042.
  47. Mohammadi M, McMahon G, Sun L, Tang C, Hirth P, Yeh BK, Hubbard SR, Schlessinger J: Structures of the tyrosine kinase domain of fibroblast growth factor receptor in complex with inhibitors. Science 1997;276:955–960.

Pay-per-View Options
Direct payment This item at the regular price: USD 38.00
Payment from account With a Karger Pay-per-View account (down payment USD 150) you profit from a special rate for this and other single items.
This item at the discounted price: USD 26.50