Janus kinase 2 gene, Tyrosine Kinase Mutation
JAK2 V617F Mutation Detection, Bone Marrow
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 variant other than the V617F may be present in an area that interferes with primer or probe binding and cause a false-negative result.
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 variant in JAK2 characterized as c.G1849T; p. Val617Phe (V617F). This variant is identified overall in approximately two-thirds of all MPN,(1-3) but the prevalence varies by MPN subtype. The JAK2 V617F variant is present in 95% to 98% of polycythemia vera patients, 50% to 60% of primary myelofibrosis (PMF) patients, and 50% to 60% of essential thrombocythemia (ET) patients. It has also been described infrequently in other myeloid neoplasms, including chronic myelomonocytic leukemia and myelodysplastic syndrome.(4) This variant is not seen in chronic myelogenous leukemia (CML) or in reactive conditions with elevated blood counts. Detection of the JAK2 V617F variant 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 variant (20%-30% of PMF and ET) and MPL exon 10 variant (5%-10% of PMF and 3%-5% of ET). Variants in JAK2, CALR, and MPL are essentially mutually exclusive.
Positive variant status is highly suggestive of a myeloid neoplasm, but must be correlated with clinical and other laboratory features for definitive diagnosis.
Negative variant 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.