Abstract
Imatinib-resistant tyrosine kinase (TK) fusions involving FGFR1, JAK2, or FLT3 are rare but recurrent in patients with eosinophilia-associated neoplasms. We report here 2 male patients with ETV6-FLT3(+) myeloid/lymphoid neoplasms with eosinophilia who were treated with the multitargeted TK inhibitors sunitinib and sorafenib. Patient 1 achieved rapid complete hematologic response and complete cytogenetic response after 3 months of taking sunitinib. A secondary blast phase caused by clonal evolution was diagnosed after 6 months. He achieved a second complete hematologic response after taking sorafenib but relapsed 2 months later. An N841K point mutation within the TK domain of FLT3, previously reported in acute myeloid leukemia and potentially conferring resistance to sorafenib, was subsequently identified. Patient 2 was heavily pretreated according to the initial diagnosis of T-lymphoblastic lymphoma and died in sunitinib-induced pancytopenia. This report highlights the importance of a careful diagnostic workup for eosinophilia-associated neoplasms to evaluate the possibility of TK inhibitor therapy.
Publication types
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Case Reports
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Amino Acid Sequence
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Antineoplastic Agents / therapeutic use
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Base Sequence
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Benzenesulfonates / therapeutic use
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DNA, Neoplasm / genetics
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Drug Resistance, Neoplasm / genetics
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ETS Translocation Variant 6 Protein
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Eosinophilia / complications
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Eosinophilia / drug therapy
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Eosinophilia / genetics
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Hematologic Neoplasms / complications
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Hematologic Neoplasms / drug therapy*
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Hematologic Neoplasms / genetics*
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Humans
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Indoles / therapeutic use
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Male
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Middle Aged
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Molecular Sequence Data
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Niacinamide / analogs & derivatives
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Oncogene Fusion
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Oncogene Proteins, Fusion / genetics*
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Phenylurea Compounds
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Point Mutation
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Protein Kinase Inhibitors / therapeutic use
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Proto-Oncogene Proteins c-ets / genetics*
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Pyridines / therapeutic use
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Pyrroles / therapeutic use
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Repressor Proteins / genetics*
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Sorafenib
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Sunitinib
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fms-Like Tyrosine Kinase 3 / antagonists & inhibitors*
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fms-Like Tyrosine Kinase 3 / genetics*
Substances
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Antineoplastic Agents
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Benzenesulfonates
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DNA, Neoplasm
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Indoles
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Oncogene Proteins, Fusion
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Phenylurea Compounds
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Protein Kinase Inhibitors
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Proto-Oncogene Proteins c-ets
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Pyridines
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Pyrroles
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Repressor Proteins
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Niacinamide
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Sorafenib
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FLT3 protein, human
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fms-Like Tyrosine Kinase 3
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Sunitinib