Abstract
Chronic eosinophilic leukemia (CEL) is a rare myeloproliferative neoplasm. Diagnosis of CEL is often challenging, notably because of the lack of recurrent and specific molecular event. We report here a case of CEL occurring in a 49-year-old man who presented a persistent hypereosinophilia (HE) associated with anemia and thrombopenia. Karyotyping showed a translocation t(5;12)(q31;p13). Targeted RNA Sequencing identified a novel ETV6::RAPGEF6 fusion gene, confirmed by RT-PCR. Despite several lines of treatment, the patient died after 16 months of duration with transformation to acute myeloid leukemia (AML).Contrary to myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions (MLN-TK), where fusion genes are both class defining and involve tyrosine kinase genes as the 3' partner, fusion genes are exceedingly rare in non-MLN-TK myeloid malignancies with HE. The most reported fusion gene is ETV6::ACSL6, in rare cases. Previously, overexpression of IL3 (interleukin 3) has been described in myeloid neoplasms with ETV6::ACSL6 (previously named ACS2). In our case of CEL with the ETV6::RAPGEF6 fusion, we also demonstrated overexpression of IL3, which could potentially result from the proximity of the IL3 gene to RAPGEF6, similar to what is observed with ACSL6 and IL3. The use of RNA sequencing in routine diagnosis of CEL could provide evidence for clonal event such as gene fusion, improving diagnosis as well as prognosis and therapeutic approaches.