Myeloproliferative Neoplasms Diagnostic Testing**

Molecular genetic screening of the JAK2, CALR and MPL genes plays a crucial role in the diagnosis, classification, and management of myeloproliferative neoplasms (MPNs). It will detect a clinically significant variant in the vast majority of patients with a classic, BCR::ABL1-negative, MPN:  Essential Thrombocythaemia (ET), Polycythaemia Vera (PV) or Primary Myelofibrosis (PMF).  The JAK2 p.(Val617Phe) variant is observed in >96% of PV, and approximately half of all ET and PMF cases. Clinically significant variants in exon 12 of the JAK2 gene are observed in most remaining PV patients.  Variants in exon 9 of the CALR gene form the second most frequent MPN driver mutation type, observed in approaching one third of ET and PMF patients, whilst variants in exon 10 of the MPL gene account for 3-11% of ET and 6-9% of PMF¹. Thus, appropriate assays targeting the four core MPN variant types, JAK2 p.(Val617Phe), JAK2 exon 12, CALR exon 9 and MPL exon 10, will identify a driver mutation in almost all PV patients and 85-90% of patients with ET and PMF¹.

The Myeloproliferative Neoplasms Diagnostic Testing programme is designed for laboratories performing MPN testing using current diagnostic algorithms² to diagnose and subtype the disease. There are four trial issues per annum, each consisting of two samples (eight samples per year). Samples will consist of either lyophilised cells or genomic DNA extracted from patient samples (full instructions will be given at trial issue). Subject to their test repertoire, participants are expected to test seven of the samples for each of the four core pathogenic MPN variant types: JAK2 p.(Val617Phe) and clinically significant variants in JAK2 exon 12, CALR exon 9 and MPL exon 10. The eighth sample will be identified as a post treatment / post hematopoietic stem cell transplant follow-up sample, requiring sensitive testing for JAK2 p.(Val617Phe) only. Please note that testing of all four regions / variant types is not mandatory if such testing is not offered by the participating laboratory; participants are only expected to return results for assays they provide. Participants will be given the opportunity to inform UK NEQAS LI of their test repertoire to ensure fair and appropriate performance monitoring.

From April 2024, the MPN Diagnostic Testing programme incorporates the JAK2 p.Val617Phe (V617F) Mutation Status (Accredited) programme.  All key features of the JAK2 p.Val617Phe (V617F) Mutation Status programme are now provided within the MPN Diagnostic Testing programme: performance monitoring for qualitative JAK2 p.(Val617Phe) testing across all eight samples and provision of z scores for optional JAK2 p.(Val617Phe) quantification in JAK2 p.(Val617Phe) positive samples, as applicable.  The JAK2 p.Val617Phe (V617F) Mutation Status programme is no longer available as a stand-alone programme.

UK NEQAS LI are currently seeking full accreditation of the MPN Diagnostic Testing programme; once achieved, performance monitoring for qualitative testing of exon 12 of JAK2, exon 9 of CALR and exon 10 of MPL will be provided.  Optional performance monitoring for quantification of the JAK2 p.(Val617Phe) variant will also be available for laboratories offering this service.

Extended next generation sequencing panel data is not included in this programme; such testing is provided within the Myeloid Gene Panels (Pilot – Not Accredited) programme. Click here

Pre issue testing of samples for this programme may be subcontracted, although the final decision about sample suitability lies with the external quality assessment provider; no other activities in relation to this EQA programme are subcontracted.

1. Cross, NCP et al. (2021) Br J Haematol 195(3):338-351

2. Tefferi, A & Pardanani, A (2014) Nat Rev Clin Oncol 11: 125–126

**The JAK2 p.V617F Mutation Status programme is now incorporated within the MPN DT programme. Please note, only the JAK2 p.V617F aspect of testing is currently accredited. We are working towards accreditation for the other markers.

To register for this programme, please click here.