t(9;12)(q22;p13) ETV6::SYK : A new recurrent cytogenetic aberration and tyrosine kinase gene fusion in myeloid or lymphoid neoplasms associated with eosinophilia

作者：Els Lierman, Sanne Smits, Koen Debackere, Marc André, Lucienne Michaux, Peter Vandenberghe · 发表于：British Journal of Haematology · 年份：2022 · DOI：10.1111/bjh.18569 · 被引用次数：9 · 研究领域：Eosinophilic Disorders and Syndromes、Mast cells and histamine、Chronic Myeloid Leukemia Treatments

Spleen tyrosine kinase (SYK), a 72 kDa cytoplasmic non-receptor protein tyrosine kinase, is expressed primarily in haematopoietic cells like B-cells, monocytes, macrophages, mast cells, and neutrophils. SYK is critical for B-cell receptor (BCR) signalling, but also has a role in the signal transduction of other receptors like Fc receptors and adhesion receptors.1 Based on this, targeted therapy with entospletinib (GS-9973) and TAK-659, oral SYK inhibitors, is being assessed in B- and T-cell malignancies, while fostamatinib (R788), and cerdulatinib (PRT062070) are being investigated in autoimmune/inflammatory disorders as rheumatoid arthritis, autoimmune haemolytic anaemia and immune thrombocytopenia.2 In addition, SYK gene fusions occur rarely in haematological malignancies. The t(5;9)(q33;q22) encoding the kinase fusion ITK::SYK is recurrent in follicular T-cell lymphoma.3, 4 A t(9;12)(q22;p13) encoding an ETV6::SYK tyrosine kinase fusion gene was reported twice so far, once in a case with an atypical myelodysplastic syndrome (MDS)5 and once in a B-lymphoblastic leukaemia.6 We here report a third case with an ETV6::SYK tyrosine kinases fusion gene. This case, originally diagnosed as a myelodysplastic/myeloproliferative neoplasm, unclassifiable7 with eosinophilia, bears remarkable resemblance to the case described by Kuno et al.5 We document sensitivity of ETV6::SYK-transformed cells in vitro to SYK inhibitors. We therefore propose to classify haematological neoplasms with ET...