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25482 Myeloproliferative Neoplasm, JAK2 V617F with Reflex to CALR and MPL, Varies

Myeloproliferative Neoplasm, JAK2 V617F with Reflex to CALR and MPL, Varies
Test Code: MPNRSO
Synonyms/Keywords
83872-JAK2B, Janus kinase 2 gene, Tyrosine Kinase Mutation, CALR Calreticulin Essential Thrombocythemia, JAK2-negative Myeloproliferative Neoplasm, Myelofibrosis, Myeloproliferative Disorder, Myeloproliferative Neoplasm (MPN), Primary Myelofibrosis, MPL S505, MPLW515, Myeloproliferative leukemia virus oncogene, JAK2 V617F with reflex to CALR and MPL (MPNR)
Test Components
​JAK2, V617F,(JAK2B), CALR (CALX), MPL (exon10) (MPLR)

Testing Algorithm:

This reflex test sequentially evaluates for the common major gene variants associated with non-BCR-ABL1-positive myeloproliferative neoplasms until a variant is identified. The testing sequence is based on the reported frequency of gene variants in this disease group. Initial testing evaluates for the presence of the JAK2 V617F variant. If this result is negative or very low positive (0.06%-2%), testing proceeds with assessment for CALR gene variants. If the CALR result is also negative, then testing proceeds to evaluate for variants in exon 10 of the MPL gene. If either JAK2 V617F (>2%) or CALR variants are detected in the process, the testing algorithm ends; therefore, the complete reflex is followed only in the event of sequential negative variant. An integrated report is issued with the summary of test results
Useful For

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

Specimen Requirements
​Specimen MUST arrive within 7 days of collection.  Sumbmit only 1 of the following specimen types:​​​​​​​​​ ​ ​ ​ ​
Specimen Type
 Preferred Container/Tube Acceptable Container/Tube Specimen Volume Specimen Minimum Volume
(allows for 1 repeat)		 Pediatric Minimum Volume
(no repeat)​​
​Whole Blood ​Lavender Top Tube (EDTA) ​Yellow Top Tube (ACD solution B) ​3 mL ​0.5 mL ​
​Bone Marrow ​Lavender Top Tube (EDTA) ​​Yellow Top Tube (ACD solution B) ​2 mL

​0.5 mL

 ​
​Extractd DNA from blood or bone marrow ​1.5  to 2 mL tube with indication of volume and concentration of DNA ​50 mcL at 20 ng/mcL concentration
 ​ ​
Collection Processing Instructions

The following information is required:
1. Pertinent clinical history
2. Clinical or morphologic suspicion
3. Date of collection
4. Specimen source

Blood and Bone Marrow:  Invert collection container several times to mix.  Send specimen in original tube.  DO NOT aliquot.  Label specimen with sample type.

Specimen must arrive within 168 hours (7 days) of collection.

Specimen Stability Information
Specimen Type Temperature Ti​​me
Whole Blood​ ​ Ambient (preferred) ​7 days
​Refrigerate ​7 days
Bone Marrow ​ ​Ambient (preferred) ​7 days
​Refrigerate ​7 days
Extraced DNA from blood or bone marrow​ ​ ​Ambient (preferred) ​7 days
​Refrigerate ​7 days
Rejection Criteria

Gross hemolysis, ​Paraffin embedded bone marrow aspirate clot or biopsy blocks, slides, or paraffin shavings, ​Moderately to severely clotted​ specimens​.

Interference

​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.

Performing Laboratory Information
Performing Location Day(s) Test Performed Analytical Time Methodology/Instrum​​entation
​Mayo Clinic Laboratories ​Monday through Friday ​7-10 days Quantitaive Polymerase Chain Reaction (qPCR)
Reference Lab
Mayo Clinic Laboratories
Test Information

​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.

Reference Range Information
An interpretive report will be provided.
Interpretation

​The results will be reported as 1 of the 4 following states:

-Positive for JAK2 V617F variant

-Positive for CALR variant

-Positive for MPL variant

-Negative for JAK2 V617F, CALR, and MPL variants

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 neoplasms.

Results below the laboratory cutoff for positivity are of unclear clinical significance currently.

Outreach CPTs
CPT Modifier
(if needed)		 Quantity Description Commen​​ts
81270 ​ ​1 ​Jak2 V617F variant ​
81219 ​ ​1 ​CALR Gene Mutation, Exon 9 ​If needed
​81339 ​ ​1 ​MPL exon 10 sequence ​If needed
Synonyms/Keywords
83872-JAK2B, Janus kinase 2 gene, Tyrosine Kinase Mutation, CALR Calreticulin Essential Thrombocythemia, JAK2-negative Myeloproliferative Neoplasm, Myelofibrosis, Myeloproliferative Disorder, Myeloproliferative Neoplasm (MPN), Primary Myelofibrosis, MPL S505, MPLW515, Myeloproliferative leukemia virus oncogene, JAK2 V617F with reflex to CALR and MPL (MPNR)
Test Components
​JAK2, V617F,(JAK2B), CALR (CALX), MPL (exon10) (MPLR)

Testing Algorithm:

This reflex test sequentially evaluates for the common major gene variants associated with non-BCR-ABL1-positive myeloproliferative neoplasms until a variant is identified. The testing sequence is based on the reported frequency of gene variants in this disease group. Initial testing evaluates for the presence of the JAK2 V617F variant. If this result is negative or very low positive (0.06%-2%), testing proceeds with assessment for CALR gene variants. If the CALR result is also negative, then testing proceeds to evaluate for variants in exon 10 of the MPL gene. If either JAK2 V617F (>2%) or CALR variants are detected in the process, the testing algorithm ends; therefore, the complete reflex is followed only in the event of sequential negative variant. An integrated report is issued with the summary of test results
Ordering Applications
Ordering Application Descri​​ption
​Centricity ​JAK2 V617F with reflex CALR and MPL (MPNR)
If the ordering application you are looking for is not listed, contact your local laboratory for assistance.
Specimen Requirements
​Specimen MUST arrive within 7 days of collection.  Sumbmit only 1 of the following specimen types:​​​​​​​​​ ​ ​ ​ ​
Specimen Type
 Preferred Container/Tube Acceptable Container/Tube Specimen Volume Specimen Minimum Volume
(allows for 1 repeat)		 Pediatric Minimum Volume
(no repeat)​​
​Whole Blood ​Lavender Top Tube (EDTA) ​Yellow Top Tube (ACD solution B) ​3 mL ​0.5 mL ​
​Bone Marrow ​Lavender Top Tube (EDTA) ​​Yellow Top Tube (ACD solution B) ​2 mL

​0.5 mL

 ​
​Extractd DNA from blood or bone marrow ​1.5  to 2 mL tube with indication of volume and concentration of DNA ​50 mcL at 20 ng/mcL concentration
 ​ ​
Collection Processing

The following information is required:
1. Pertinent clinical history
2. Clinical or morphologic suspicion
3. Date of collection
4. Specimen source

Blood and Bone Marrow:  Invert collection container several times to mix.  Send specimen in original tube.  DO NOT aliquot.  Label specimen with sample type.

Specimen must arrive within 168 hours (7 days) of collection.

Specimen Stability Information
Specimen Type Temperature Ti​​me
Whole Blood​ ​ Ambient (preferred) ​7 days
​Refrigerate ​7 days
Bone Marrow ​ ​Ambient (preferred) ​7 days
​Refrigerate ​7 days
Extraced DNA from blood or bone marrow​ ​ ​Ambient (preferred) ​7 days
​Refrigerate ​7 days
Rejection Criteria

Gross hemolysis, ​Paraffin embedded bone marrow aspirate clot or biopsy blocks, slides, or paraffin shavings, ​Moderately to severely clotted​ specimens​.

Interference

​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.

Useful For

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

Test Components
​JAK2, V617F,(JAK2B), CALR (CALX), MPL (exon10) (MPLR)

Testing Algorithm:

This reflex test sequentially evaluates for the common major gene variants associated with non-BCR-ABL1-positive myeloproliferative neoplasms until a variant is identified. The testing sequence is based on the reported frequency of gene variants in this disease group. Initial testing evaluates for the presence of the JAK2 V617F variant. If this result is negative or very low positive (0.06%-2%), testing proceeds with assessment for CALR gene variants. If the CALR result is also negative, then testing proceeds to evaluate for variants in exon 10 of the MPL gene. If either JAK2 V617F (>2%) or CALR variants are detected in the process, the testing algorithm ends; therefore, the complete reflex is followed only in the event of sequential negative variant. An integrated report is issued with the summary of test results
Reference Range Information
An interpretive report will be provided.
Interpretation

​The results will be reported as 1 of the 4 following states:

-Positive for JAK2 V617F variant

-Positive for CALR variant

-Positive for MPL variant

-Negative for JAK2 V617F, CALR, and MPL variants

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 neoplasms.

Results below the laboratory cutoff for positivity are of unclear clinical significance currently.

For more information visit:
Performing Laboratory Information
Performing Location Day(s) Test Performed Analytical Time Methodology/Instrum​​entation
​Mayo Clinic Laboratories ​Monday through Friday ​7-10 days Quantitaive Polymerase Chain Reaction (qPCR)
Reference Lab
Mayo Clinic Laboratories
For billing questions, see Contacts
Outreach CPTs
CPT Modifier
(if needed)		 Quantity Description Commen​​ts
81270 ​ ​1 ​Jak2 V617F variant ​
81219 ​ ​1 ​CALR Gene Mutation, Exon 9 ​If needed
​81339 ​ ​1 ​MPL exon 10 sequence ​If needed
For most current information refer to the Marshfield Laboratory online reference manual.