Comprehensive response criteria for myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions: a proposal from the MLN International Working Group

Abstract

In 2008, in response to the identification of patients with “chronic eosinophilic leukemia” or “hypereosinophilic syndrome” who carried recurrent tyrosine kinase fusion genes involving PDGFRA , PDGFRB , or FGFR1 , the World Health Organization classification of myeloid neoplasms included a new category termed “Myeloid/lymphoid neoplasms (MLN) with eosinophilia and rearrangements of PDGFRA, PDGFRB , or FGFR1 ” [ 1 ]. This World Health Organization category was revised in 2016 with the addition of PCM1::JAK2 as a provisional entity [ 1 ]. In the recent fifth edition of the World Health Organization classification, similar to the recent update to the International Consensus Classification, the category was renamed to “myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions” and both classifications added novel subtypes with new JAK2 rearrangements (e.g., BCR::JAK2 , ETV6::JAK2 ) as well as fusions involving FLT3 , and the ETV6 :: ABL1 fusion [ 2 , 3 ]. Although eosinophilia (>0.5 × 10 9 /l) or hypereosinophilia (>1.5 × 10 9 /l) are characteristic of this subgroup, they are not universally present [ 4 ]. The clinical phenotype is largely influenced by the involved tyrosine kinase fusion gene and/or the fusion partner gene [ 5 , 6 ]. For example, most patients with the FIP1L1::PDGFRA fusion gene present with a chronic myeloid neoplasm with eosinophilia; however, mixed lineage presentations are more common in patients with FGFR1 fusions [ 5 , 6 , 7 , 8 ]. Furthermore, in MLN with FGFR1 rearrangements, translocations involving ZMYM2 are more commonly associated with a T-lymphoblastic lymphoma phenotype, whereas translocations involving BCR tend to lead to a phenotype resembling BCR::ABL1 positive chronic myeloid leukemia [ 5 , 6 , 9 ].

Topics & Concepts