JAK2 V617F Mutation Detection, Blood
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
The Janus kinase 2 gene (JAK2) codes for a tyrosine kinase (JAK2) that is associated with the cytoplasmic portion of a variety of transmembrane cytokine and growth factor receptors important for signal transduction in hematopoietic cells. Signaling via JAK2 activation causes phosphorylation of downstream signal transducers and activators of transcription (STAT) proteins (eg, STAT5) ultimately leading to cell growth and differentiation. BCR-ABL1-negative myeloproliferative neoplasms (MPN) frequently harbor an acquired single nucleotide mutation in JAK2 characterized as c.G1849T; p. Val617Phe (V617F). This mutation is identified overall in approximately two-thirds of all MPN,(1-3) but the prevalence varies by MPN subtype. The JAK2 V617F is present in 95% to 98% of polycythemia vera, 50% to 60% of primary myelofibrosis, and 50% to 60% of essential thrombocythemia. It has also been described infrequently in other myeloid neoplasms, including chronic myelomonocytic leukemia and myelodysplastic syndrome.(4) This mutation is not seen in chronic myelogenous leukemia (CML) or in reactive conditions with elevated blood counts. Detection of the JAK2 V617F is useful to help establish the diagnosis of MPN. However, a negative JAK2 V617F result does not indicate absence of a MPN. Other important molecular markers in BCR-ABL1-negative MPN include CALR exon 9 mutation (20%-30% of PMF and ET) and MPL exon 10 mutation (5%-10% of PMF and 3%-5% of ET).(5-9) Mutations in JAK2, CALR, and MPL are essentially mutually exclusive.
Aiding in the distinction between a reactive blood cytosis and a chronic myeloproliferative disorder
The results will be reported as 1 of the 2 states:
-Negative for JAK2 V617F mutation
-Positive for JAK2 V617F mutation
Positive mutation status is highly suggestive of a myeloid neoplasm, but must be correlated with clinical and other laboratory features for definitive diagnosis.
Negative mutation status does not exclude the presence of a myeloproliferative neoplasm or other neoplasm.
Results below the laboratory cutoff for positivity are of unclear clinical significance at this time.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
A positive result is not specific for a particular subtype of myeloproliferative neoplasm and clinicopathologic correlation is necessary in all cases. If this test is ordered in the setting of erythrocytosis and suspicion of polycythemia vera, interpretation requires correlation with a concurrent or recent prior bone marrow evaluation.
A negative result does not exclude the presence of a myeloproliferative neoplasm or other neoplastic process.
In rare cases, a mutation other than the V617F may be present in an area that interferes with primer or probe binding and cause a false-negative result.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
An interpretive report will be provided.
Clinical References Provides recommendations for further in-depth reading of a clinical nature
1. Baxter EJ, Scott LM, Campbell PJ, et al: Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet 2005 March 16;365(9464):1054-1061
2. James C, Ugo V, Le Couedic JP, et al: A unique clonal JAK2 mutation leading to constitutive signaling causes polycythaemia vera. Nature 2005 April 28;434(7037):1144-1148
3. Kralovics R, Passamonti F, Buser AS, et al: A gain-of-function mutation of JAK2 in myeloproliferative disorders. N Engl J Med 2005;352:1779-1790
4. Steensma DP, Dewald GW, Lasho TL, et al: The JAK2 V617F activating tyrosine kinase mutation is an infrequent event in both "atypical" myeloproliferative disorders and the myelodysplastic syndrome. Blood 2005;106:1207-1209