Myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase fusion genes

Myeloid/lymphoid neoplasm with eosinophilia and tyrosine kinase fusion genes (MLN-TK) include hematological neoplasms with rearrangements/fusion genes of the tyrosine kinases PDGFRA (e.g., FIP1L1::PDGFRA), PDGFRB (e.g., ETV6::PDGFRB), FGFR1 (e.g., ZMYM2::FGFR1), JAK2 (e.g., PCM1::JAK2), ABL1 (e.g., ETV6::ABL1), and very rarely FLT3 (e.g., ETV6::FLT3). The complex diagnosis requires nearly all available molecular genetic technologies including specific RT-PCR (reverse transcriptase polymerase chain reaction) and FISH (fluorescence in situ hybridization) analyses, conventional cytogenetics, and NGS (next generation sequencing). Clinically, these entities are variably associated with an underlying myeloid neoplasm and a primary or secondary blast phase of myeloid or lymphoid origin, with manifestation in the bone marrow or extramedullary. While eosinophilia is present in > 90-95 % of patients with FIP1L1::PDGFRA and ETV6::ABL1 fusion genes, it may be absent in other subtypes. Eosinophilia > 1.5 x 10(9)/l is frequently associated with monocytosis > 1 x 10(9)/l, regardless of subtype. The prognosis of MLN with PDGFRA/-B fusion genes is excellent due to their rapid and durable responses to the tyrosine kinase inhibitor (TKI) imatinib with long-term complete hematological and molecular remissions even in blast phase. The possibility of imatinib discontinuation with long-term therapy-free remissions has been reported. In contrast, MLN with FGFR1, JAK2, ABL1 and FLT3 fusion genes are frequently associated with primary blast phase or rapid transformation into secondary blast phase and a mostly inadequate response to the available therapeutic options and a poor prognosis. Recently developed TKI with and without subsequent allogeneic stem cell transplantation are promising.