Katherine Moore¹, Emily Jude¹, Aleisha Jaffrey¹, Michael Krigstein¹.
¹St Vincent's Hospital, Darlinghurst, NSW, Australia

Background: Up to 5-10% of myeloproliferative neoplasms (MPN) are so-called ‘triple-negative’, lacking a canonical JAK2, CALR and MPL mutation.(1)  Traditionally, diagnosing MPNs involves targeted testing of JAK2 V617F, CALR fragment analysis and MPL W515. Next-generation sequencing (NGS) offers rapid, broad assessment of these genes, potentially uncovering diagnostic mutations that previous methods would miss.  

Aim: To determine if NGS can identify driver mutations in MPNs that previous testing methods would have missed.

Methods: We reviewed JAK2, CALR, and MPL mutations identified by myeloid NGS testing in all patients investigated for potential MPNs at a single laboratory in NSW between October 2023 and October 2024.  

Results: From the 580 NGS tests undertaken to investigate potential MPNs, we identified JAK2, CALR or MPL mutations in 258 patients.  Two JAK2 exon 12, one JAK2 exon 14 indel variant and three MPL diagnostic mutations would not have been identified by traditional testing. 11 CALR variants were identified that were not classic 52bp type 1 deletions or 5bp type 2 insertions.  A further three JAK2 and five MPL variants of unclear significance were identified.

Discussion: Identifying a driver mutation is crucially important in diagnosing MPNs.  NGS allows for the discovery of non-canonical mutations, enhancing diagnostic accuracy.

References
1. Rumi E and Cazzola M. Diagnosis, risk stratification and response evaluation in classical myeloproliferative neoplasms. Blood 2017; 129: 680-692.
 
Authorship:

Katherine Moore: conceptualisation, investigation, methodology, writing – original draft. Emily Jude: conceptualisation, data curation, methodology, writing – review and editing. Aleisha Jaffrey: data curation. Michael Krigstein: supervision, writing – review and editing.