Evaluation includes assessment for reactive causes of eosinophilia (vasculitis such as eosinophilic granulomatosis and polyangiitis or Churg-Strauss, parasitic infection, autoimmune disease, immunoglobulinG4-related disease, medications and other causes), genetic lesions characteristic of clonal myeloid disorders (platelet-derived growth factor receptor-α, platelet-derived growth factor receptor-β and fibroblast growth factor receptor 1) and flow cytometry and molecular studies for the aberrant T cells characteristic of lymphocyte-variant HES .
In the present report, we describe three new cases of AML associated with FGFR1 abnormalities: AML with minimal differentiation with 45,XY,-7,t(8;13)(p11.2;q12), acute myelomonocytic leukemia with eosinophilia with 48,XY,t(8;9)(p11.2;q33),+19,+21, and AML with minimal differentiation with 46,XX,add(8)(p11.2).
Important changes include (1) the change of nomenclature of myeloproliferative disorder to myeloproliferative neoplasm emphasizing the clonal nature of these disorders; (2) the classification of mast cell disease as an MPN; (3) the reorganization of the eosinophilic disorders into a molecularly defined category of PDGFRA, PDGFRB and FGFR1-associated myeloid and lymphoid neoplasms with eosinophilia and chronic eosinophilic leukemia, not otherwise specified; and (4) refinement of the diagnostic criteria for PV, ET and PMF incorporating recently described molecular markers, JAK2V617F, JAK2 exon 12 mutations and MPL mutations.
We conclude that neither the SCLL phenotype nor blood eosinophilia is a consistent feature of FGFR1-associated 8p11.2 translocations; conversely, FISH might not always reveal FGFR1 involvement in typical SCLL.
8p11 myeloproliferative syndrome preceded by t(8;9)(p11;q33), CEP110/FGFR1 fusion transcript: morphologic, molecular, and cytogenetic characterization of myeloid neoplasms associated with eosinophilia and FGFR1 abnormality.
HES and CEL-NOC are considered distinct from molecularly defined eosinophilic disorders, such as those associated with activating mutations of PDGFR (PDGFRA and PDGFRB) and fibroblast growth factor receptor-1.
Rearrangements of the genes encoding the fibroblast growth factor receptor 1 (FGFR1) and platelet-derived growth factor receptors (PDGFR) alpha or beta receptor tyrosine kinases are found in a rare but important subset of patients with atypical myeloproliferative disorders that are usually but not always associated with eosinophilia.
Rearrangements involving PDGFRA and PDGFRB in eosinophilic chronic myeloproliferative disorders, and of fibroblast growth factor receptor 1 (FGFR1) in the 8p11 stem cell myeloproliferative syndrome constitute additional examples of specific genetic alterations linked to clonal eosinophilia.
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.