Chronic Eosinophilic Leukaemia Associated with <b><i>JAK2</i></b> Exon 13 Insertion/Deletion Mutations

Abstract

Chronic eosinophilic leukaemia, not otherwise specified (CEL, NOS), is a diagnosis of exclusion made in cases in which there is clonal eosinophilia but an absence of genetic aberrations that define other disease subtypes. There is a need for further characterization of these cases in order to inform risk stratification and management. The importance of &lt;i&gt;JAK2&lt;/i&gt; mutations in myeloproliferative neoplasms (MPN) as a whole is well established, although their role specifically in eosinophilic disorders is less clear, with only a minority of cases demonstrating &lt;i&gt;JAK2&lt;/i&gt; abnormalities. Here, we report 2 cases with an exon 13 insertion-deletion (indel) mutation in &lt;i&gt;JAK2:&lt;/i&gt; one with CEL-NOS and the second with an unspecified eosinophilic disorder. &lt;i&gt;JAK2&lt;/i&gt; indels were not detected in a screen of suspected MPN cases (&lt;i&gt;n&lt;/i&gt; = 592) without eosinophilia that tested negative for common MPN driver mutations. Our findings thus provide further evidence for a specific association between this rare mutation and clonal eosinophilic disorders.

JAK2 R683S Mutation Resulting in Dual Diagnoses of Chronic Eosinophilic Leukemia and Myelodysplastic/Myeloproliferative Overlap Syndrome

“…Somatic JAK2 ex13InDel mutations occurring in isolation have been described in CEL, but the absence of additional molecular abnormalities may be more reflective of the limits of clinical NGS panels. 18 As outlined in this report and in prior studies, 3 dual disease phenotypes that meet histopathologic criteria for both CEL and either MPN or MDS/MPN appear to carry an exceptionally high risk of thrombosis that is in large part driven by clonal hypereosinophilia. 3 These rare cases appear to be highly associated with non-V617F somatic JAK2 mutations such as JAK2 ex13InDel and JAK2 R683S.…”