Chronic eosinophilic leukemia

By demonstrating eosinophilia, cytomorphology represents a central role in the diagnosis of chronic eosinophilic leukemia (CEL). In addition, it can help to exclude differential diagnoses that may also cause eosinophilia.

For CEL, no specific immunophenotype has been described. Nevertheless, immunophenotyping is important for the exclusion of T cell-associated eosinophilia.

No specific chromosomal aberrations have been described for CEL. However, chromosomal analysis may be important for clonality detection by demonstrating cytogenetic alterations, thereby allowing differentiation from idiopathic hypereosinophilic syndrome (HES). Various numerical and structural chromosomal alterations were described that have also occur in other myeloid neoplasms. These include, for example, trisomy 8, monosomy 7, an isochromosome 17q, 13q and 20q deletions, and alterations of chromosome 1. Complex karyotypes may also occur (Morsia et al. 2020, Qu et al. 2025).

In the diagnosis of CEL, FISH analysis is used, for example, to exclude the presence of MLN-TK (i.g. specific PDGFRA, PDGFRB, JAK2, and FGFR1 rearrangements). Due to the high number of partner genes, FISH analysis is more suitable than molecular genetics for excluding these rearrangements. Moreover, it can be used as a complementary method to classical chromosome analysis to answer specific questions.

Molecular genetics is used in the diagnosis of chronic eosinophilic leukemia (CEL) firstly to exclude other hematologic neoplasms. In this regard, screening for increased PDGFRA expression as surrogate for PDGFRA rearrangements, as well as detection for a FIP1L1::PDGFRA fusion transcript and the ETV6::ABL1 fusion, is performed to exclude the entity "myeloid/lymphoid neoplasms with eosinophilia and defining genetic rearrangements". On the other hand, the diagnosis of CEL requires the detection of clonality. The clonality detection of molecular genetic alterations allows the differentiation from an idiopathic hypereosinophilic syndrome (HES). For this purpose, analyses are performed for KIT p.D816V, JAK2 p.V617F, JAK2 exon 13, and STAT5B p.N642H mutations, which are mutated in 1% to 4% of cases with hypereosinophilia (WHO 2022). Multicenter data from Yin et al. show that STAT5B mutations occur at a frequency of 15% in CEL and are present as dominant/co-dominant clones in 83% of cases (Yin et al. 2024).

If further clonality analysis is desired, next-generation sequencing would be desirable to examine a myeloid gene panel. Mutations described in CEL include mutations in the genes ASXL1, IDH1, IDH2, TP53, SRSF2, SH2B3, TET2, SETBP1, SF3B1, EZH2, CBL, and NF1 (Reiter & Gotlib 2017, Morsia et al. 2020). However, in the elderly, mutations can occur without association to hematologic neoplasia. If mutations with a mutational burden of ≥2% can be detected in genes typically mutated in myeloid neoplasms in the absence of signs of hematologic neoplasia and absence of cytopenia, clonal hematopoiesis of undetermined potential (CHIP in hematology) is present. The most commonly affected genes in this regard are TET2, ASXL1, and DNMT3A (Steensma 2018). Therefore, these genes should be critically considered for clonality detection in the diagnosis of chronic eosinophilic leukemia (WHO 2022).