[The 8p11 myeloproliferative syndrome]

Abstract

Clinical manifestations: The 8p11 myeloproliferative syndrome is characterized by a chronic myelogenous leukemia-like myeloid hyperplasia, marked eosinophilia and a strikingly high incidence of non-Hodgkin's lymphoma, mostly of the T-lymphoblastic subtype. After a short chronic phase of 6 to 9 months it rapidly transforms into an acute myelogenous leukemia. The median survival time is less than 12 months.

Cytogenetics: The leukemic cells of peripheral blood/bone marrow and the lymphoma cells have the same acquired, clonal abnormality of chromosome band 8p11 with the translocations t(8;13)(p11;q12), t(8;9)(p11;q34), and t(6;8)(q27;p11).

Molecular genetics: The molecular cloning of these translocations has shown the fusion of three unrelated genes (ZNF198 at 13p12, FAN at 9q34 and FOP at 6q27) to the fibroblast growth factor receptor-1 (FGFR1) gene at 8p11. The complete coding sequence of the tyrosine kinase domain of FGFR1 is retained in all three fusion genes and presumably activated by sequences of the different fusion partners by dimerization.

Conclusion: Activation of tyrosinc kinase signal transduction pathways are of increasing interest in the pathogenesis of chronic myeloproliferative disorders and myelodysplastic syndromes. The development of tyrosine kinase inhibitors could represent a promising therapeutic tool.