ETV6/FLT3 fusion gene detected in a patient with T-cell lymphoblastic lymphoma

Genetic alterations of the gene FLT3, especially internal tandem duplications in the juxtamembrane domain and point mutations in the tyrosine kinase domain, are commonly seen in patients with newly diagnosed myeloid leukemias. The fused 5' end of ETV6 encodes the helix-loop-helix domain (exons 3 and 4), the internal domain (exon 5), and part of the ETS domain (exons 6-8), whereas the fused 3' end of FLT3 includes the transmembrane domain (TMD) and the tyrosine kinase domain (TKD) (Fig. 1C). Furthermore, ETV6 fusions could also contribute to leukemogenesis by modifying the original functions of fused transcription factors, including the loss of transcriptional repression mediated by wildtype ETV6.3A Rearrangements of ETV6 with other tyrosine kinase encoding genes such as ABL1 and FGFR1 are among described drivers of clonal eosinophilia.3^ With the growing list of recurrent rearrangements associated with eosinophilia, rearrangements involving PDGFRA/B and EGER1, or the PCM1-JAK2 rearrangement, are now recognized by the 2016 WHO classification of hematopoietic tumors as part of the diagnostic criteria for myeloid/lymphoid neoplasms with eosinophilia.8 The importance of the timely identification of these rearrangements lies in the potential response to tyrosine kinase inhibitor therapy. Which of the following statements is true about FLT3? a. FLT3 mutations are identified in about five percent of patients with newly diagnosed myeloid leukemias. b. FLT3-ITD indicates the internal tandem duplications in the tyrosine kinase domain. c. FLT3 activators have been approved for dinical use, leading to therapeutic paradigms for AML with FLT3 mutations. d. It is recommended to screen for FLT3 mutations by the National Comprehensive Cancer Network guidelines for new acute leukemia cases. 2.