**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.
Programme objective To assess a laboratory’s ability to accurately conduct molecular genetic testing for the four core variant types associated with myeloproliferative neoplasms (MPNs): JAK2 p.(Val617Phe), and clinically significant variants in exon 12 of JAK2, exon 9 of CALR and exon 10 of MPL.
Clinical/scientific background Molecular genetic screening of the JAK2, CALR and MPL genes plays a crucial role in the diagnosis, classification, and management of 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 adriver mutation in almost all PV patients and 85-90% of patients with ET and PMF1.
Suitability Any molecular genetic approach for the detection of JAK2 p.(Val617Phe) and clinically significant variants in JAK2 exon 12, CALR exon 9 and MPL exon 10. 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 are given the opportunity to inform UK NEQAS LI of their test repertoire to ensure fair and appropriate performance monitoring. Participants should submit a qualitative result for each of the tests their laboratory offers; for positive results, there is the option to submit a quantitative result (variant allele burden), however this is neither obligatory, nor currently subject to performance monitoring.
Sample type/distribution Four trials are issued per annum, each featuring two samples (eight samples per year). Samples will either be lyophilised cell line derived material 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 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. The trial schedule can be found here: https://www.ukneqasli.co.uk/eqa-pt-programmes/trial-schedules/
Trial duration Trials for this programme are live/open for a minimum of four weeks. Please note, trials issued/closing in August or December are extended by one week. An automated email is sent two days prior to the trial closing, to any participant that has not returned results, warning them of the trial closure date.
Subcontracted areas Pre-issue and post-closure testing of samples for this programme is subcontracted, although the final decision about sample suitability lies with the EQA provider; no other activities in relation to this EQA programme are subcontracted.
Updates to the programme for current or upcoming year From April 2024, the MPN Diagnostic Testing programme incorporated the now obsolete 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: UKAS accredited performance monitoring for qualitative JAK2 p.(Val617Phe) testing across all eight samples, as well as provision of z scores for optional variant 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.
1. Cross, NCP et al. The use of genetic tests to diagnose and manage patients with myeloproliferative and myeloproliferative/myelodysplastic neoplasms, and related disorders. Br J Haematol 195(3):338-351 (2021).
To register for this programme, please click here.