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HelpMayo Test ID CALX CALR Mutation Analysis, Myeloproliferative Neoplasm (MPN), Reflex, Varies
Specimen Required
Only orderable as a reflex. For more information see MPNR / Myeloproliferative Neoplasm, JAK2 V617F with Reflex to CALR and MPL, Varies.
Useful For
Aiding in the distinction between a reactive cytosis and a chronic myeloproliferative disorder
Evaluating mutations in CALR in an algorithmic process for the MPNR / Myeloproliferative Neoplasm, JAK2 V617F with Reflex to CALR and MPL, Varies
Method Name
Only orderable as a reflex. For more information see MPNR / Myeloproliferative Neoplasm, JAK2 V617F with Reflex to CALR and MPL, Varies.
Polymerase Chain Reaction (PCR) and Fragment Analysis
Reporting Name
CALR, Gene Mutation, Exon 9, ReflexSpecimen Type
VariesSpecimen Minimum Volume
Blood and Bone Marrow: 1 mL
Specimen Stability Information
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| Varies | Varies | 7 days |
Reject Due To
| Gross hemolysis | Reject |
| Paraffin embedded bone marrow aspirate clot or biopsy blocks, slides, paraffin shavings Moderately to severely clotted |
Reject |
Clinical Information
The JAK2 (Janus kinase 2) gene codes for a tyrosine kinase (JAK2) 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 mutation in JAK2 characterized as c.G1849T; p. Val617Phe (V617F). The JAK2 V617F is present in 95% to 98% of polycythemia vera, 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 mutation (20%-30% of PMF and ET) and MPL exon 10 mutation (5%-10% of PMF and 3%-5% of ET). Mutations in JAK2, CALR, and MPL are essentially mutually exclusive. A CALR mutation 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 Values
Only orderable as a reflex. For more information see MPNR / Myeloproliferative Neoplasm, JAK2 V617F with Reflex to CALR and MPL, Varies.
An interpretive report will be provided.
Interpretation
An interpretation will be provided under the MPNR / Myeloproliferative Neoplasm, JAK2 V617F with Reflex to CALR and MPL, Varies.
Cautions
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 mutation other than the V617F may be present in an area that interferes with primer or probe binding and cause a false-negative result.
Method Description
Polymerase chain reaction (PCR) amplification of CALR exon 9 is performed on DNA isolated from the patient sample. The PCR product is then run on an ABI Genetic Analyzer for fragment analysis to detect insertions and deletions. An unmutated CALR will show an amplicon at 266 base pairs (bp), a mutated CALR with insertion will show an amplicon greater than 266 bp, and a mutated CALR with deletion will show an amplicon smaller than 266 bp. This assay has an analytical sensitivity of approximately 6% (ie, 6 mutation-containing cells in 100 total cells) in most mutation types, except for the rare type of 1-bp deletion, which has a sensitivity of approximately 20%.(Unpublished Mayo method)
Day(s) Performed
Monday through Friday
Report Available
7 to 10 daysSpecimen Retention Time
Whole blood, bone marrow: 2 weeks; Extracted DNA 3 monthsPerforming Laboratory
Mayo Clinic Laboratories in Rochester
Test Classification
This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.CPT Code Information
81219-CALR (calreticulin) (eg, myeloproliferative disorders), gene analysis, common variants in exon 9
LOINC Code Information
| Test ID | Test Order Name | Order LOINC Value |
|---|---|---|
| CALX | CALR, Gene Mutation, Exon 9, Reflex | 77174-1 |
| Result ID | Test Result Name | Result LOINC Value |
|---|---|---|
| 36998 | Final Diagnosis | 22637-3 |
Clinical Reference
1. Klampfl T, Gisslinger H, Harutyunyan AS, et al. Somatic mutation of calreticulin in myeloproliferative neoplasms. N Engl J Med. 2013;369(25):2379-2390
2. Nangalia J, Massie CE, Baxter EJ, et al. Somatic CALR mutation in myeloproliferative neoplasms with nonmutated JAK2. N Engl J Med. 2013;369(25):2391-2405
3. Rumi E, Pietra D, Ferretti V, et al. JAK2 or CALR mutation status defines subtypes of essential thrombocythemia with substantially different clinical course and outcomes. Blood. 2014;123(10):1544-1551
4. Rotunno G, Mannarelli C, Guglielmelli P, et al. Impact of calreticulin mutations on clinical and hematological phenotype and outcome in essential thrombocythemia. Blood. 2014;123(10):1552-1555
5. Tefferi A, Lasho TL, Finke CM, et al. CALR vs JAK2 vs MPL-mutated or triple-negative myelofibrosis: clinical, cytogenetic and molecular comparisons. Leukemia. 2014;28(7):1472-1477