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

Test Code

PVJAK

Alias/See Also

Epic: LAB13826
Mayo: PVJAK

JAK2 V617F
JAK2 exon 12
Polycythemia Vera
Myeloproliferative Neoplasm (MPN)

CPT Codes
81270-JAK2 V617 0027U (if appropriate)

Includes

REFLEX TESTS

Test Id	Reporting Name	Available Separately	Always Performed
JAKXR	JAK2 Exon 12-15 Sequencing, Reflex	Yes, (order JAKXB-blood or JAKXM-bone marrow), Bill Only	No

TESTING ALGORITHM

Both DNA and RNA are extracted. The algorithm starts with a highly sensitive DNA-based JAK2 V617F test by allele specific polymerase chain reaction. If the JAK2 V617F result is negative or very low positive (0.06%-0.6%), JAK2 exon 12-15 Sanger sequencing will be performed on the stored RNA sample. If a JAK2 V617F mutation (>0.6%) is detected, no further testing will be performed.

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. For more information, the following algorithms are available:

-Erythrocytosis Evaluation Testing Algorithm
-Myeloproliferative Neoplasm: A Diagnostic Approach to Bone Marrow Evaluation
-Myeloproliferative Neoplasm: A Diagnostic Approach to Peripheral Blood Evaluation

Preferred Specimen

Submit only 1 of the following specimens:

Specimen Type: Blood
Container/Tube: Lavender top (EDTA) or yellow top (ACD-B)
Specimen Volume: 10 mL
Collection Instructions:
1. Invert several times to mix blood.
2. Send whole blood specimen in original tube. Do not aliquot.
3. Label specimen as blood.

Specimen Type: Bone marrow aspirate
Container/Tube: Lavender top (EDTA) or yellow top (ACD-B)
Specimen Volume: 4 mL
Collection Instructions:
1. Invert several times to mix blood.
2. Send bone marrow specimen in original tube. Do not aliquot.
3. Label specimen as bone marrow.

Minimum Volume

Blood: 8 mL
Bone Marrow: 2 mL

Transport Temperature

Refrigerated

Specimen Stability

Specimen Type	Temperature	Time	Special Container
Varies	Refrigerated (preferred)	5 days
	Ambient	5 days

Reject Criteria (Eg, hemolysis? Lipemia? Thaw/Other?)

Gross hemolysis
Paraffin-embedded bone marrow aspirate clot or biopsy blocks
Slides
Paraffin shavings
Moderately to severely clotted

Methodology
Allele-Specific Polymerase Chain Reaction (AS-PCR) and Sanger Sequencing

Setup Schedule

Monday through Friday

Report Available

7 to 10 days

Limitations

CAUTIONS
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.

Reference Range

REFERENCE VALUES

An interpretive report will be provided.

INTERPRETATION

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.

Clinical Significance

USEFUL FOR

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

CLINICAL INFORMATION

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 mutation is located in exon 14 and present in 50% to 60% of primary myelofibrosis and essential thrombocythemia and in 95% to 98% of polycythemia vera (PV). In the rest of the PV 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 PV. These mutations include point alterations 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.

Performing Laboratory
Mayo Clinic Laboratories - Rochester
3050 Superior Drive NW
Rochester, MN 55901

Additional Information
Polycythemia Vera, JAK2 V617F with Reflex to JAK2 Exon 12-15, Sequencing for Erythrocytosis, Varies

Last Updated: June 23, 2023
Last Review: N. Wolford, June 23, 2023

The CPT Codes provided in this document are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payor being billed. Any Profile/panel component may be ordered separately. Reflex tests are performed at an additional charge.