8p11 myeloproliferative syndrome: a review

SummaryThe 8p11 myeloproliferative syndrome is an aggressive neoplasm associated with chromosomal translocations involving the fibroblast growth factor receptor 1 tyrosine kinase gene on chromosome 8p11-12. By our count, 65 cases are currently reported in the literature. This neoplasm affects patients of all ages, with a slight male predominance. Patients often present with peripheral blood eosinophilia without basophilia. Bone marrow examination commonly is hypercellular, with or without eosinophilia, which usually leads to the initial diagnosis of a myeloproliferative neoplasm. Many patients also present with or develop lymphadenopathy. Lymph node biopsy in these patients has commonly shown lymphoblastic leukemia/lymphoma, most often reported as being of T-cell lineage, but bilineal myeloid/T-cell lymphomas and less often a myeloid sarcoma are also reported. The natural history of this neoplasm is to evolve into acute leukemia, usually of myeloid or mixed lineage, and less frequently of T- or B-lymphoid lineage. The prognosis is poor despite aggressive chemotherapy, with a few patients achieving long clinical remission after stem cell transplantation. At the molecular level, all cases carry a chromosomal abnormality involving the fibroblast growth factor receptor 1 (FGFR1) gene at chromosome 8p11, where 10 translocations and 1 insertion have been identified. These abnormalities disrupt the FGFR1 and various partner genes, and result in the creation of novel fusion genes and chimeric proteins. The latter include the N-terminal portion of the partner genes and the C-terminal portion of FGFR1. The most common partner is ZNF198 on chromosome 13q12. In the current World Health Organization classification, the 8p11 myeloproliferative syndrome is designated as “myeloid and lymphoid neoplasms with FGFR1 abnormalities.”