title: Response of ETV6-FLT3-positive myeloid/lymphoid neoplasm with eosinophilia to inhibitors of FMS-like tyrosine kinase 3.
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.
authors.affiliation: Pathologisches Institut, Ludwig-Maximilians-Universität, München, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Walz
authors.forename: Philipp
authors.initials: P
authors.lastname: Erben
authors.forename: Michael
authors.initials: M
authors.lastname: Ritter
authors.forename: Adrian
authors.initials: A
authors.lastname: Bloor
authors.forename: Georgia
authors.initials: G
authors.lastname: Metzgeroth
authors.forename: Nick
authors.initials: N
authors.lastname: Telford
authors.forename: Claudia
authors.initials: C
authors.lastname: Haferlach
authors.forename: Torsten
authors.initials: T
authors.lastname: Haferlach
authors.forename: Stefan
authors.initials: S
authors.lastname: Gesk
authors.forename: Joannah
authors.initials: J
authors.lastname: Score
authors.forename: Wolf-Karsten
authors.initials: WK
authors.lastname: Hofmann
authors.forename: Andreas
authors.initials: A
authors.lastname: Hochhaus
authors.forename: Nicholas C P
authors.initials: NC
authors.lastname: Cross
authors.forename: Andreas
authors.initials: A
authors.lastname: Reiter
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001483:Base Sequence; D001557:Benzenesulfonates / Q000627:therapeutic use; D004273:DNA, Neoplasm / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D004802:Eosinophilia / Q000150:complications / Q000188:drug therapy / Q000235:genetics; D019337:Hematologic Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000235:genetics*; D006801:Humans; D007211:Indoles / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009536:Niacinamide / Q000031:analogs & derivatives; D050596:Oncogene Fusion; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D010671:Phenylurea Compounds; D017354:Point Mutation; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D050783:Proto-Oncogene Proteins c-ets / Q000235:genetics*; D011725:Pyridines / Q000627:therapeutic use; D011758:Pyrroles / Q000627:therapeutic use; D012097:Repressor Proteins / Q000235:genetics*; D000077157:Sorafenib; D000077210:Sunitinib; D051941:fms-Like Tyrosine Kinase 3 / Q000037:antagonists & inhibitors* / Q000235:genetics*; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D004273:DNA, Neoplasm; D007211:Indoles; D009536:Niacinamide; D015514:Oncogene Proteins, Fusion; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D050783:Proto-Oncogene Proteins c-ets; D011725:Pyridines; D011758:Pyrroles; D012097:Repressor Proteins; D000077157:Sorafenib; D000077210:Sunitinib; D051941:fms-Like Tyrosine Kinase 3; D000097764:ETS Translocation Variant 6 Protein; C497970:FLT3 protein, human