Aiding in the distinction between a reactive cytosis and a chronic myeloproliferative disorder
Evaluating for variants in JAK2, CALR, and MPL genes in an algorithmic process
The following information is required: 1. Pertinent clinical history 2. Clinical or morphologic suspicion 3. Date of collection 4. Specimen source
Specimen must arrive within 168 hours (7 days) of collection.
Send whole blood or bone marrow specimens in original tube. Label must indicate sample type.
A positive result is not specific for a particular subtype of myeloproliferative neoplasm and clinicopathologic correlation is necessary in all cases.
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.
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.
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). The JAK2 V617F is present in 95% to 98% of polycythemia vera (PV), and 50% to 60% of primary myelofibrosis (PMF) and essential thrombocythemia (ET). It has also been described infrequently in other myeloid neoplasms, including chronic myelomonocytic leukemia and myelodysplastic syndrome. Detection of the JAK2 V617F is useful to help establish the diagnosis of MPN. However, a negative JAK2 V617F result does not indicate the absence of 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. A CALR variant is associated with decreased risk of thrombosis in both ET and PMF, and confers a favorable clinical outcome in PMF patients. A triple negative (JAK2 V617F, CALR, and MPL-negative) genotype is considered a high-risk molecular signature in PMF.