The 8p11 Myeloproliferative Syndrome: A Distinct Clinical Entity Caused by Constitutive Activation of FGFR1Macdonald 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
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.
Prof. N.C.P. Cross
Wessex Regional Genetics Laboratory
Salisbury District Hospital
Salisbury, SP2 8BJ (UK)
Tel. +44 1722 429080, Fax +44 1722 338095, E-Mail email@example.com
Number of Print Pages : 7
Number of Figures : 1, Number of Tables : 1, Number of References : 47
Affiliated with Molecular Biology of Hematopoiesis Symposium
Vol. 107, No. 2, Year 2002 (Cover Date: Released March 2002)
Journal Editor: I. Ben-Bassat, Tel Hashomer
ISSN: 0001–5792 (print), 1421–9662 (Online)
For additional information: http://www.karger.com/journals/aha