Myeloid Neoplasms with t(5;12) and ETV6-ACSL6 Gene Fusion, Potential Mimickers of Myeloid Neoplasm with PDGFRB Rearrangement: Case Report with Imatinib Therapy and Review of the Literature

Abstract

We report the second case of ETV6-ACSL6 associated myeloproliferative neoplasm that has received a full course of imatinib therapy. The patient was a 51-year-old previously healthy man who presented with three months of worsening dyspnea and was found to have a white count of 216,000/cmm, of which 84% were eosinophil lineage. Cytogenetic analysis revealed a t(5;12)(q31~33;p13). FISH was negative for PDGFRB rearrangement but additional FISH testing demonstrated an ACSL6 rearrangement. ETV6-ACSL6 gene fusion is a rare abnormality that most often presents as a myeloproliferative-type disorder with prominent eosinophilia or basophilia. Review of the literature yielded a total of 11 previous cases. This gene fusion results in a t(5;12)(q31~33;p13) that mimics the t(5;12) found in ETV6-PDGFRB neoplasms. Identification of the fusion genes involved in t(5;12) in eosinophilia-associated myeloproliferative disorders is crucial to direct an effective treatment plan. In particular, while tyrosine kinase inhibitor therapy is effective in patients with PDGFRB rearrangement, there is little information on imatinib efficacy in patients with ETV6-ACSL6 gene fusion. Our patient was found to be nonresponsive to imatinib therapy.

ETV6-ACSL6 fusion gene in myeloid neoplasms: clinical spectrum, current practice, and outcomes

“…Among patients with chronic myeloid disorders, many had chronic eosinophilic leukemia, NOS, and others suffered from MDS, MDS/MPN, and MPN. In addition, we found that the majority of the patients had increased eosinophils in peripheral blood [3,5,7]. Additionally, our study revealed that 80% of patients also had increased basophils in peripheral blood.…”

“…The demographic characteristics, clinical symptoms and diagnosis, treatment, and outcomes of the sixteen patients are listed in Table 1 , and one presented with a complex karyotype involving 5q and 12p [11]. Treatments using tyrosine kinase inhibitors were ineffective, including imatinib (n = 4) and sorafenib (n = 2) [3,10,11]. Hydroxyurea was used in 58% of patients and sometimes led to temporary decreases in eosinophils and improvement of anemia and clinical symptoms [10].…”

“…The present case is the 16th case reported so far. The demographic characteristics, clinical symptoms and diagnosis, treatment, and outcomes of the sixteen patients are listed in Table 1 [ 2 , 3 , 5 – 11 ]. Twelve patients were male, with a median age of 50 years (range, 27–71 years).…”

“…Translocations involving band 12p13 are frequently seen in myeloid malignancies, through which ETV6 is frequently rearranged [1,2]. However, fusion of ETV6 with ACSL6 is very rarely reported, and the clinical characteristics, proper treatment strategies, and effect on prognosis are poorly understood [3]. The prognosis of patients with the ETV6-ACSL6 fusion gene is thought to be rather poor, with most patients surviving less than a year [3].…”

“…However, fusion of ETV6 with ACSL6 is very rarely reported, and the clinical characteristics, proper treatment strategies, and effect on prognosis are poorly understood [3]. The prognosis of patients with the ETV6-ACSL6 fusion gene is thought to be rather poor, with most patients surviving less than a year [3]. To expand the current knowledge of the ETV6-ACSL6 fusion gene, we reported a patient with the ETV6-ACSL6 fusion gene who presented with chronic eosinophilic leukemia, not otherwise specified (NOS), who importantly received proper treatment regimens and consequently had a good prognosis.…”