Test Catalog

Test ID: PVJAK    
Polycythemia Vera, JAK2 V617F with Reflex to JAK2 Exon 12-15, Sequencing for Erythrocytosis, Varies

Useful For Suggests clinical disorders or settings where the test may be helpful

Aiding in the distinction between the myeloproliferative neoplasm polycythemia vera (PV) and other secondary erythrocytosis

Testing Algorithm Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

Both DNA and RNA are extracted. The algorithm starts with a highly sensitive DNA-based JAK2 V617F test by allele-specific PCR. If a JAK2 V617F mutation is detected, the algorithm stops and no further testing will be performed. If no JAK2 V617F mutation is detected, JAK2 exon 12-15 Sanger sequencing test will be performed on the stored RNA sample. The Sanger sequencing covers JAK2 exons 12 through the first 90% of exon 15, which spans the region containing essentially all mutations reported in myeloproliferative neoplasms.

 

The following algorithms are available in Special Instructions.

-Erythrocytosis Evaluation Testing Algorithm

-Myeloproliferative Neoplasm: A Diagnostic Approach to Bone Marrow Evaluation

-Myeloproliferative Neoplasm: A Diagnostic Approach to Peripheral Blood Evaluation

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

The Janus kinase 2 (JAK2) gene 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. The JAK2 V617F is located in exon 14 and present in 50% to 60% of primary myelofibrosis and essential thrombocythemia, and 95% to 98% of polycythemia vera (PV). In the rest of the polycythemia vera cases, over 50 different mutations have been reported within exons 12 through 15 of JAK2 and essentially all of the non-V617F JAK2 mutations have been identified in polycythemia vera. These mutations include point mutations and small insertions or deletions. Several of the exon 12 mutations have been shown to have biologic effects similar to those caused by the V617F mutation such that it is currently assumed other nonpolymorphic mutations have similar clinical effects. However, some mutations may not be well characterized and requires further clinical and research evaluation.

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.

Interpretation Provides information to assist in interpretation of the test results

The results will be reported as 1 of the 3 following states:

-Positive for JAK2 V617F mutation

-Positive for JAK2 mutation (other than V617F)

-Negative for JAK2 mutations

 

If the result is positive, a description of the mutation at the nucleotide level and the altered protein sequence are reported.

 

A positive mutation status is highly suggestive of a myeloid neoplasm and may support a diagnosis of polycythemia vera in the appropriate clinical setting. Correlation with clinicopathologic findings and other laboratory results is necessary in all cases.

 

A negative mutation status makes a diagnosis of polycythemia vera highly unlikely, although it does not completely exclude this possibility, other myeloproliferative neoplasms or other neoplasms.

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 diagnosis. Correlation with clinicopathologic findings and other laboratory results 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.

Clinical Reference Recommendations for 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

5. Ma W, Kantarjian H, Zhang X, et al: Mutation profile of JAK2 transcripts in patients with chronic myeloid neoplasias. J Mol Diagn 2009;11:49-53

6. Kilpivaara O, Levine RL: JAK2 and MPL mutations in myeloproliferative neoplasms: discovery and science. Leukemia 2008;22:1813-1817

7. Kravolics R: Genetic complexity of myeloproliferative neoplasms. Leukemia 2008;22:1841-1848

Special Instructions Library of PDFs including pertinent information and forms related to the test