Abstract
BACKGROUND Myeloid neoplasms with [em]ETV6::ACSL6[/em] fusions are extremely rare entities that are characterized by eosinophilic and/or basophilic leukocytosis. While they clinically mimic myeloid neoplasms with eosinophilia and tyrosine kinase fusions such as [em]ETV6::PDGFRB[/em], they have not been shown to be responsive to imatinib. There are currently no effective treatments available and clinical outcomes are poor. CASE REPORT We report a rare case of a 71-year-old man with a history of myelodysplastic syndrome/neoplasms (MDS) with mutated [em]SF3B1[/em] and multilineage dysplasia treated with luspatercept followed by azacitidine. However, he developed clonal evolution of disease to MDS with hypereosinophilia. Chromosome analysis identified t(5;12)(q31;p13). Fluorescence in situ hybridization was negative for [em]FIP1L1/PGFFRA[/em] or [em]PDGFRB[/em] gene rearrangement, but RNA-sequencing identified the [em]ETV6::ACSL6[/em] fusion. He received a hematopoietic cell transplantation with achievement of complete remission but subsequently relapsed, with chromosome analysis again revealing t(5;12)(q31;p13) [[em]ETV6::ACSL6[/em]]. He rapidly clinically deteriorated and developed refractory respiratory failure due to acute eosinophilic pneumonitis. He received a prolonged course of high-dose steroids without adequate improvement of the eosinophilia. Based on reports showing good response to tyrosine kinase inhibitors in patients with the [em]ETV6::PDGFRB[/em] fusion, treatment was switched to imatinib, leading to rapid normalization of absolute eosinophil counts, with clinical improvement. CONCLUSIONS Our findings suggest that imatinib should be considered for patients with a myeloid neoplasm with an [em]ETV6::ACSL6[/em] fusion who are refractory to corticosteroids. Further molecular investigations are needed to elucidate the underlying mechanism of imatinib sensitivity in [em]ETV6::ASCL6[/em]-associated disease, given the absence of genetic involvement of a tyrosine kinase.