Myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase fusion genes: A workshop report with focus on novel entities and a literature review including paediatric cases

Abstract

Myeloid/lymphoid neoplasms with eosinophilia (M/LN‐eo) and tyrosine kinase (TK) gene fusions are a rare group of haematopoietic neoplasms with a broad range of clinical and morphological presentations. Paediatric cases have increasingly been recognised. Importantly, not all appear as a chronic myeloid neoplasm and eosinophilia is not always present. In addition, standard cytogenetic and molecular methods may not be sufficient to diagnose M/LN‐eo due to cytogenetically cryptic aberrations. Therefore, additional evaluation with fluorescence in‐situ hybridisation and other molecular genetic techniques (array‐based comparative genomic hybridisation, RNA sequencing) are recommended for the identification of specific TK gene fusions. M/LN‐eo with JAK2 and FLT3‐rearrangements and ETV6::ABL1 fusion were recently added as a formal member to this category in the International Consensus Classification (ICC) and the 5th edition of the WHO classification (WHO‐HAEM5). In addition, other less common defined genetic alterations involving TK genes have been described. This study is an update on M/LN‐eo with TK gene fusions with focus on novel entities, as illustrated by cases submitted to the Bone Marrow Workshop, organised by the European Bone Marrow Working Group (EBMWG) within the frame of the 21st European Association for Haematopathology congress (EAHP‐SH) in Florence 2022. A literature review was performed including paediatric cases of M/LN‐eo with TK gene fusions.

Rare Hematologic Malignancies and Pre-Leukemic Entities in Children and Adolescents Young Adults

“…This rare group of myeloid malignancies was previously known as chronic eosinophilic leukemia (CEL) or idiopathic hypereosinophilic syndrome (HES). They are characterized by a clonal proliferation of myeloid and eosinophilic cells and are associated with gene fusions involving PDGRA , PDGFRB , FGFR1 , or a protein tyrosine kinase such as JAK2 (e.g., PCM-JAK2 ), resulting in constitutively active tyrosine kinase and proliferation of the abnormal clone [ 153 ]. Clinicopathologic presentation is heterogenous.…”

“…Clinicopathologic presentation is heterogenous. Leukocytosis with eosinophilia, anemia, hepatosplenomegaly, lymphadenopathy, and skin lesions (rashes, ulcers) have been reported in children aged 0 to 14 years [ 153 ].…”

“…Treatment often involves a tyrosine kinase inhibitor (TKI) with or without chemotherapy and/or HSCT [ 153 ].…”

Hematological Neoplasms with Eosinophilia

“…Significantly, the majority of patients are male, and the illness occurs at any stage of life [47][48][49][50][51]. The main characteristics of the different categories of M/LN-eo with eosinophilia are summarized in Table 3.…”

“…The limited number of patients, their clinical heterogeneity, and the short follow-up make the choice of therapeutic approaches challenging. Targeted therapy with JAK2 inhibitors, such as ruxolitinib, may be beneficial by inducing hematologic or molecular improvement of benefit [77,104,105], but allogeneic stem cell transplantation is considered the only curative option [50].…”