Functional Characterization of Two Rare BCR-FGFR1 Leukemias

Overview

Journal Cold Spring Harb Mol Case Stud

Specialty Genetics

Date 2020 Jan 26

PMID 31980503

Citations 4

Authors

Evan J Barnes

Jessica Leonard

Bruno C Medeiros

Brian J Druker

Cristina E Tognon

Affiliations

Soon will be listed here.

Abstract

8p11 myeloproliferative syndrome (EMS) represents a unique World Health Organization (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 acute myeloid leukemia (AML) or T- or B-lymphoblastic lymphoma/leukemia. Within the EMS subtype, translocations between () and () have been shown to produce a dominant fusion protein that is notoriously resistant to tyrosine kinase inhibitors (TKIs). Here, we report two cases of EMS identified via RNA sequencing (RNA-seq) and confirmed by fluorescence in situ hybridization (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-cell acute lymphoblastic leukemia (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, whereas 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.

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