Dear Editor, The ETV6 gene, previously known as TEL, is a member of the ETS family of transcription factors located at 12p13. Its role in leukemogenesis was initially estabilished as a fusion partner to the PDGFR-beta gene in a case of chronic myelomonocytic leukemia with t (5;12)(q33;p13) [1]. The ETV6-ABL gene product has been demonstrated to have tyrosine kinase activity remarkably similar to that of BCR-ABL, despite the fusion partners for ABL being completely different [2]. Several studies proved the efficacy of imatinib for patients with hypereosinophilic syndrome (HES) and chronic eosinophilic leukemia (CEL), especially in those who express the FIP1L1-PDGFRα fusion gene [3–5]. As development of resistance or intollerance to Imatinib in these patients may parallel that seen in chronic myeloid leukemia (CML), the evaluation of second-generation tyrosine kinase inhibitors (TKIs), such as nilotinib, has been reported [6]. However, to date, little is known on long-term efficacy and safety of secondgeneration TKIs after imatinib failure in patients with eosinophilic neoplasms. A 65-year-oldmalewas found to have hemoglobin 13.0 g/dL, platelets 302×10/μL, leukocytes 16.7×10/μL, with 65 % neutrophilis, 3 %metamyelocytes, 3 %myelocytes, 10 % eosinophils, 8 % basophils, 8 % lymphocytes, and 3 % monocytes. The physical exam was negative. Bone marrow biopsy and aspirate were consistent with a chronic phase myeloproliferative neoplasm (MPN). Karyotype was 46,XY,t(9;12)(q34;p12); molecular analysis was negative for BCR/ABL and for rearrangements involving PDGFRα andβ and FIP1L1 gene, while showing a fusion between ETV6 and ABL genes. The patient was enrolled in a protocol testing imatinib for HES, starting in May 2005 at a dose of 100 mg daily, with weekly dose escalation up to 400 mg/day. The patient attained a complete hematologic response (CHR) at 1 month and a complete cytogenetic response (CCyR) at 6 months. In January 2006, the patient complained an olfactory dysfunction (dysosmia). An ear, nose, and throat (ENT) visit and central nervous system RMN scan were negative; so supposing a possible imatinib toxicity, the drug was stopped with a slight improvement of olfactory function. There was a progressive increase in eosinophil count; so in June 2006, imatinib was restarted at 100 mg daily and progressively increased up to 400 mg, at which dose dysosmia recurred. In December 2006, while receiving imatinib 400 mg, despite persistent olfactory dysfunction, the patient lost CHR. To investigate imatinib resistance, a mutational study of ABL kinase domain was performed, without evidence of any mutation. In October 2007, the patient started nilotinib 400 mg twice a day. The patient attained CHR within 2 weeks and regained CCyR and molecular remission at 6 months that were confirmed at the 12 months of therapy and at all the molecular testing performed thereafter. Five years after initiation of nilotinib, the patient developed signs of peripheral arterial occlusive disease (PAOD) of the lower limbs that required angioplasty and surgical treatment of the skin lesions. Nilotinib was reduced to 400 mg/day. In June 2014, almost 7 years from nilotinib start; and while in confirmed complete molecular remission, the patient complained of abdominal pain and weight loss. An abdominal CT scan revealed a pancreatic carcinoma that caused the patient’s death in September 2014. * Mario Tiribelli mario.tiribelli@uniud.it