A novel TRIP11-FLT3 fusion in a patient with a myeloid/lymphoid neoplasm with eosinophilia

Alfred Chung; Yanli Hou; Robert S Ohgami; Ann Von Gehr; Dianna G Fisk; Krishna M Roskin; Xu Li; Linda Gojenola; Charles D Bangs; Daniel A Arber; Andrew Z Fire; Athena M Cherry; James L Zehnder; Jason Gotlib; Jason D Merker

doi:10.1016/j.cancergen.2017.05.001

A novel TRIP11-FLT3 fusion in a patient with a myeloid/lymphoid neoplasm with eosinophilia

Cancer Genet. 2017 Oct:216-217:10-15. doi: 10.1016/j.cancergen.2017.05.001. Epub 2017 May 10.

Authors

Affiliations

¹ Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
² Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
³ Kaiser Permanente, San Jose Medical Group, San Jose, CA 95119, USA.
⁴ Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
⁵ Molecular Genetic Pathology Service, Stanford Health Care, Stanford, CA 94305, USA.
⁶ Cytogenetics Laboratory, Stanford Health Care, Stanford, CA 94305, USA.
⁷ Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA; Division of Hematology, Stanford University School of Medicine/Stanford Cancer Institute, Stanford, CA, USA.
⁸ Division of Hematology, Stanford University School of Medicine/Stanford Cancer Institute, Stanford, CA, USA.
⁹ Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: [email protected].

PMID: 29025582
DOI: 10.1016/j.cancergen.2017.05.001

Abstract

FLT3 fusions are associated with myeloid and lymphoid neoplasms with eosinophilia. We describe a patient presenting with clinicopathologic features of both chronic eosinophilic leukemia, not otherwise specified (CEL, NOS) and systemic mastocytosis (SM). The bone marrow demonstrated a myeloproliferative neoplasm with eosinophilia and aggregates of atypical mast cells. Cytogenetic analysis revealed a t(13;14)(q12;q32), which was subsequently molecularly characterized as a novel TRIP11-FLT3 rearrangement. A KIT D816V mutation was also identified. The patient rapidly transformed to T-lymphoblastic leukemia/lymphoma and expired shortly after diagnosis. This is the fifth FLT3 fusion gene described in the literature; the presence of both myeloid and lymphoid neoplasms implicates involvement of an early hematopoietic progenitor by rearranged FLT3. We suggest that leukemias and lymphomas with FLT3 fusion genes exhibit similar clinicopathologic features to, and should be included in, the WHO category of "Myeloid and lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA, PDGFRB, or FGFR1, or with PCM1-JAK2."

Keywords: ACVRL1 1039G>C; ACVRL1 Ala347Pro; FLT3 rearrangement; KIT D816V; TRIP11.

Publication types

Case Reports

MeSH terms

Adult
Aged
Eosinophilia / complications*
Female
Humans
Lymphoma / complications*
Lymphoma / genetics*
Male
Middle Aged
Myeloproliferative Disorders / complications*
Myeloproliferative Disorders / genetics*
Oncogene Proteins, Fusion / genetics*
fms-Like Tyrosine Kinase 3 / genetics*

Substances

Oncogene Proteins, Fusion
TRIP11-FLT3 fusion protein, human
fms-Like Tyrosine Kinase 3