Two MLN-TK patients with ETV::ABL1 fusions mediated by different mechanisms with false negative FISH results resolved with RNA fusion analysis

Abstract

Myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase fusions (MLN-TK) is a newly added entity in the World Health Organization (WHO) 5^th Edition, and within this category, ETV6::ABL1 gene fusions are the most commonly reported in the literature. While patients may respond favorably to tyrosine kinase inhibitor (TKI) therapy, prognosis is generally less favorable than for BCR::ABL1-positive chronic myelogenous leukemia (CML), also treated with tyrosine kinase inhibitor therapy (TKIs). We report two patients diagnosed with MLN-TK, both of whom were positive for ETV6::ABL1 gene fusions, albeit by different mechanisms but with the same breakpoints. Importantly, one of our subjects also demonstrated BCR::ABL1 fusion subclonally to the ETV6::ABL1 fusion positive clone. This study emphasizes the importance of resolving false negative and/or discrepant fluorescence in situ hybridization (FISH) results using alternative methods, such as RNA fusion analysis, to aid in the diagnosis of MLN-TK.