1. ¹III. Medizinische Universitätsklinik, Fakultät für Klinische Medizin Mannheim der Universität Heidelberg, Germany
2. ²Wessex Regional Genetics Laboratory, Salisbury, UK
3. ³Human Genetics Division, University of Southampton, UK
4. ⁴Medizinische Klinik III, Klinikum Grohadern, Ludwig-Maximilians-Universität München, Germany
5. ⁵St-Antonius-Hospital, Eschweiler, Germany
6. ⁶Pathologisches Institut, Universität Freiburg, Germany

Correspondence: Dr A Reiter, III. Medizinische Universitätsklinik, Fakultät für Klinische Medizin Mannheim der Universität Heidelberg, Wiesbadener Str. 7-11, 68305 Mannheim, Germany. Fax: +49 621 383 4201; E-mail: andreas.reiter@med3.ma.uni-heidelberg.de

Received 22 November 2004; Accepted 21 January 2005; Published online 31 March 2005.

Abstract

The 8p11 myeloproliferative syndrome (EMS) also known as stem cell leukemia-lymphoma syndrome (SCLL) is associated with translocations that disrupt FGFR1. The resultant fusion proteins are constitutively active tyrosine kinases, and different FGFR1 fusions are associated with subtly different disease phenotypes. We report here a patient with a t(8;17)(p11;q23) and an unusual myelodysplastic/myeloproliferative disease (MDS/MPD) characterized by thrombocytopenia due to markedly reduced size and numbers of megakaryocytes, with elevated numbers of monocytes, eosinophils and basophils. A novel mRNA fusion between exon 32 of the myosin XVIIIA gene (MYO18A) at chromosome band 17q11 and exon 9 of FGFR1 was identified. Partial characterization of the genomic breakpoints in combination of bubble-PCR with fluoresence in situ hybridization revealed that the t(8;17) arose from a three-way translocation with breaks at 8p11, 17q11 and 17q23. MYO18A–FGFR1 is structurally similar to other fusion tyrosine kinases and is likely to be the causative transforming lesion in this unusual MDS/MPD.