Mutation Assay : JAK2 and MPL
In 2005 a novel somatic point mutation (V617F) in the conserved autoinhibitory pseudokinase domain of the Janus kinase 2 (JAK2) protein (encoded on chromosome 9p24) was described. This mutation is present in patients with myeloproliferative neoplasms at various frequencies (PV=97%, ET=50% and MF=50%). Since the discovery of JAK2 V617F as a clonal marker of MPN several other mutations have been described in this patient group and occur at differing frequencies. Notably mutations of JAK2 exon 12 and mutations of MPL (c-MPL) at codon 515.
JAK2 exon 12 mutations appear to be restricted to cases of PV, no cases of ET or MF have been described harbouring JAK2 exon 12 mutations. Conversely MPL mutations are restricted to ET and MF and have not been described in PV patients.
JAK2 Mutation Analysis at King's College Hospital
KCH have a long-standing research interest in MPD. We were the first to show that JAK2 mutations occur in about 50% of Budd Chiari Syndrome patients (Patel et al 2006) and have published a number of articles documenting the incidence of JAK2 mutations in various haematological malignancies (Lea et al 2006, Ingram et al 2006 and Ceesay et al 2006).
JAK2 V617F mutations are detected using a quantitative real time PCR (Q-PCR) based assay in the LMH laboratory which has a sensitivity of around 0.2%.
MPL W515K/L mutations are detected using a sensitive allele specific PCR reaction with a sensitivity around 1%
JAK2 exon 12 mutations are detected using a modified sequencing approach with a sensitivity around 1%
Due to the rarity of MPL and JAK2 exon 12 mutations these laboratory tests are not normally performed without a previous JAK2V617F negative result and a strong suspicion of an MPN. Exon 12 and MPL assays can be performed on the original JAK2V617F DNA sample. It is not necessary to send an additional sample to perform these analyses. Please contact the laboratory to arrange this additional analysis.
Samples must be clearly labelled with the patient's first name, surname, D.O.B, hospital number and the date the sample was taken.
London SE5 9RS
Blood Sciences Laboratory
Ground Floor Bessemer Wing
King’s College Hospital
London SE5 9RS
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Tefferi A. The diagnosis of polycythemia vera: new tests and old dictums. Best Pract Res Clin Haematol. 2006;19(3):455-69.
Tefferi A and Barbui T. bcr/abl-negative, classic myeloproliferative disorders: diagnosis and treatment. Mayo Clin Proc. 2005 Sep;80(9):1220-32
Baxter EJ. and Scott LM. Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet. 2005 Mar 19-25;365(9464):1054-61
Patel R, Lea NC. et al. Prevalence of the activating JAK2 tyrosine kinase mutation V617F in the Budd-Chiari syndrome Gastroenterology. 2006 Jun;130(7):2031-8.
Lea NC, Lim Z. et al. Presence of JAK2 V617F tyrosine kinase mutation as a myeloid-lineage-specific mutation in chronic neutrophilic leukaemia. Leukemia. 2006 Jul;20(7):1324-6.
Ingram W. Lea NC. et al. The JAK2 V617F mutation identifies a subgroup of MDS patients with isolated deletion 5q and a proliferative bone marrow. Leukemia. 2006 Jul;20(7):1319-21.
Ceesay Lea NC. et al. The JAK2 V617F mutation is rare in RARS but common in RARS-T. Leukemia. 2006 Aug 24; [Epub ahead of print]
Swerdlow SH, Campo E, et al (Eds) WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. IARC:Lyon 2008
Last updated: 07/08/2015