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Die 8p11-myeloproliferative Erkrankung

The 8p11 myeloproliferative syndrome

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Zusammenfassung

□ Klinik

Die 8p11-myeloproliferative Erkrankung ist durch eine der chronischen myeloischen Leukämie ähnliche myeloische Hyperplasie, deutliche Eosinophilie sowie ein mit hoher Inzidenz auftretendes Non-Hodgkin-Lymphom, meist vom T-lymphoblastischen Subtyp, gekennzeichnet. Nach einer kurzen chronischen Phase von durchschnittlich sechs bis neun Monaten kommt es zu einem raschen Übergang in eine akute myeloische Leukämie. Die mediane Überlebenszeit beträgt weniger als zwölf Monate.

□ Zytogenetik

In den leukämischen Zellen des peripheren Blutes/Knochenmarks und in den Zellen der Lymphknoten kann eine erworbene, klonale Abnormalität der Chromosomenbande 8p11 mit den Translokationen t(8;13) (p11;q12), t(8;9)(p11;q34) und t(6;8)(q27;p11) nachgewiesen werden.

□ Molekularbiologie

Die molekulargenetische Charakterisierung dieser Translokationen zeigt die Fusion von drei nicht miteinander verwandten Genen (ZNF198 auf 13p12, FAN auf 9q34 und FOP auf 6q27) mit dem auf 8p11 lokalisierten Gen „fibroblast growth factor receptor-1” (FGFR1). Die Tyrosinkinasedomäne von FGFR1 ist in jedem Fusionsgen komplett erhalten und vermutlich durch Dimerisierungsdomänen der unterschiedlichen Fusionspartner in identischer Weise aktiviert.

□ Schlußfolgerung

Aktivierte Tyrosinkinasen-Signaltransduktionskaskaden erlangen zunehmende Bedeutung in der Pathogenese chronischer myeloproliferativer Erkrankungen und myelodysplastischer Syndrome. Die Entwicklung von Tyrosinkinaseinhibitoren könnte daher einen, vielversprechenden therapeutischen Ansatz darstellen.

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 tyrosine 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.

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Authors and Affiliations

  1. Department of Haematology, Imperial College School of Medicine, London, UK

    John M. Goldman & Nicholas C. P. Cross

  2. III. Medizinische Klinik, Klinikum Mannheim gGmbH, Fakultät für Klinische Medizin der Universität Heidelberg, Wiesbadener Straße 7-11, D-68305, Mannheim

    Andreas Reiter & Rüdiger Hehlmann

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Correspondence to Andreas Reiter.

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Reiter, A., Hehlmann, R., Goldman, J.M. et al. Die 8p11-myeloproliferative Erkrankung. Med Klin 94, 207–210 (1999). https://doi.org/10.1007/BF03044856

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