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Vol. 107, No. 2, 2002
Issue release date: March 2002
Acta Haematol 2002;107:101–107
(DOI:10.1159/000046639)

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

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Abstract

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.



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