Whole exome sequencing analysis of a patient with myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions with ETV6::LYN fusion gene.

ETV6::LYN fusion gene is recognized as one of the genetic alterations responsible for myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions (MLN-TK) according to the 2022 WHO classification. However, the clinical features and pathogenesis of MLN-TK with ETV6::LYN are not well defined because of the rarity of the disease. Here, we report an MLN-TK patient with ETV6::LYN that manifested as myeloproliferative neoplasms (MPN) with eosinophilia, myelofibrosis, and T-lymphoblastic lymphoma (T-LBL), which eventually led to acute myeloid leukemia. Targeted RNA sequencing of both lymph node specimens diagnosed with T-LBL and bone marrow specimens diagnosed with MPN specimens detected an identical ETV6::LYN fusion gene. Whole exome sequencing (WES) detected several identical missense and nonsense mutations in both specimens. Detected mutations were not found to be relevant to pathogenesis of T-LBL and MPN in previous reports and were considered variants of uncertain significance. Based on the WES results, ETV6::LYN fusion gene was considered the driver gene essential for the pathogenesis of MPN-TK with ETV6::LYN.
Competing Interests: Declarations. Disclosure: S.F. received honoraria from Otsuka Pharmaceutical Co. Ltd. S.M. received honoraria from Bristol Myers Squibb Co., Ltd. K.K. received research funding and honoraria from Otsuka Pharmaceutical Co. Ltd. K.I. received research funding, consulting fees, and honoraria from Bristol Myers Squibb Co., Ltd. The other authors declare no competing financial interests. Informed consent: Informed consent was obtained from the patient for publication. Competing interests: The authors declare no competing interests.
(© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)