Distinction of eosinophilic leukaemia from idiopathic hypereosinophilic syndrome by analysis of Wilms' tumour gene expression

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Abstract
In patients presenting with immature eosinophilic precursors it is notoriously difficult to distinguish acute eosinophilic leukaemia (EoL) from the benign idiopathic hypereosinophilic syndrome (HES), based on morphological, cytochemical and immunophenotyping criteria, alone. Cytogenetic analysis or fluorescence in situ hybridization (FISH) can help in discriminating between these rare haematological disorders, but often treatment decisions cannot wait for the results of these time-consuming techniques. Recently, we and others found Wilms' tumour (WT1) gene expression to be increased in virtually all patients with acute leukaemias, whereas normal haemopoietic progenitors express the WT1 gene at much lower levels or not at all. To determine whether detection of WT1 gene expression is useful to distinguish EoL from HES patients, we analysed, by RT-PCR, bone marrow or blood mononuclear cells from EoL (n=3), HES (n=3) and reactive eosinophilia patients (n = 4) for WT1 gene expression. Using our WT1-RT-PCR protocol, we found WT1 gene expression to be restricted to EoL patients. By detecting WT1 mRNA transcripts in the cerebrospinal fluid using RT-PCR, we were also able to diagnose isolated CNS-relapsed leukaemia, initially confused with bacterial meningitis, in an EoL patient. In conclusion, we show that WT1-RT-PCR is a powerful complementary diagnostic tool to distinguish acute eosinophilic leukaemia from the hypereosinophilic syndromes. This observation needs confirmation in a larger series of EoL and HES patients.