Abstract

8p11 myeloproliferative syndrome (EMS) represents a unique WHO-classified hematologic malignancy defined by translocations of the FGFR1 receptor. The syndrome is a myeloproliferative neoplasm characterized by eosinophilia and lymphadenopathy, with risk of progression to either AML (acute myeloid leukemia) or T or B-lymphoblastic lymphoma/leukemia. Within the EMS subtype, translocations between Breakpoint Cluster Region (BCR) and Fibroblast Growth Factor Receptor 1 (FGFR1) have been shown to produce a dominant fusion protein that is notoriously resistant to tyrosine kinase inhibitors (TKIs). Here, we report two cases of BCR-FGFR1+ EMS identified via RNA-seq and confirmed by FISH. Sanger sequencing revealed that both cases harbored the exact same breakpoint. In the first case, the patient presented with AML-like disease, and in the second, the patient progressed to B-ALL. Additionally, we observed that that primary leukemia cells from Case 1 demonstrated sensitivity to the tyrosine kinase inhibitors Ponatinib and Dovitinib that can target FGFR1 kinase activity, while primary cells from Case 2 were resistant to both drugs. Taken together these results suggest that some but not all BCR-FGFR1 fusion positive leukemias may respond to TKIs that target FGFR1 kinase activity.

View details for DOI 10.1101/mcs.a004838

View details for PubMedID 31980503