JAK2 E12-15 + CALR + MPL NGS Panel

CPT: 81219; 81279; 81338
Updated on 09/24/2024
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Expected Turnaround Time

7 days


Specimen Requirements


Specimen

Whole blood or bone marrow


Volume

3 to 5 mL whole blood or 1 to 2 mL bone marrow


Minimum Volume

3 mL whole blood or 1 mL bone marrow


Container

Lavender-top (EDTA) tube, green-top (sodium heparin) tube, yellow-top (ACD) tube, tan-top (K2-EDTA) tube or pink-top (K2-EDTA) tube


Collection

Submit at room temperature. Specimens should arrive in the laboratory within 48 hours of collection. Indicate date and time of collection on test request form.


Storage Instructions

Ship at room temperature. If specimen is to be stored prior to shipment, store at 2°C to 8°C.


Causes for Rejection

Specimen does not meet all of the criteria for sample type, container, minimum volume, collection and storage; frozen whole blood or marrow; leaking tube; clotted blood or marrow; grossly hemolyzed or otherwise visibly degraded; contamination by another specimen; specimen containing foreign material


Test Details


Use

The JAK2 (Janus kinase 2) gene encodes for a non-receptor protein tyrosine kinase that activates cytokine and growth factor signaling. The V617F (c.1849 G>T) mutation results in constitutive activation of JAK2 and downstream STAT5 and ERK signaling. The V617F mutation is observed in approximately 95% of polycythemia vera (PV), 60% of essential thrombocythemia (ET) and primary myelofibrosis (PMF). It is also infrequently present (3-5%) in myelodysplastic syndrome, chronic myelomonocytic leukemia and other atypical chronic myeloid disorders. A small percentage of JAK2 mutation-positive patients (3.3%) contain other non-V617F mutations within exons 12 to 15. In particular, mutations in exon 12 of JAK2 have been described in approximately 3% of patients with PV. JAK2 allele burden correlates with clinical phenotype, with low levels of mutant allele characterized by thrombocytosis, intermediate levels with erythrocytosis and high mutant allele burden, correlating with enhanced myelopoiesis of the BM, leukocytosis, increasing spleen size and circulating CD34-positive cells.

The CALR (Calreticulin) gene encodes for a multifunctional calcium-binding protein involved in many cellular activities such as growth, proliferation, adhesion and programmed cell death. Among patients with JAK2-negative MPNs, CALR mutations are found in approximately 70% of patients with JAK2-negative essential thrombocythemia (ET) and 60-88% of patients with JAK2-negative primary myelofibrosis (PMF). Only a minority of patients (approximately 8%) with myelodysplasia have mutations in the CALR gene. CALR mutations are rarely detected in patients with de novo acute myeloid leukemia, chronic myelogenous leukemia, lymphoid leukemia or solid tumors. CALR mutations are not detected in polycythemia and generally appear to be mutually exclusive with JAK2 mutations and MPL mutations. The majority of mutational changes involve a variety of insertion or deletion mutations in exon 9 of the calreticulin gene: approximately 53% of all CALR mutations are a 52 bp deletion (type-1) while the second most prevalent mutation (approximately 32%) contains a 5 bp insertion (type-2). Other mutations (non-type 1 or type 2) are seen in a small minority of cases. CALR mutations in PMF tend to be associated with a favorable prognosis compared to JAK2V617F mutations, whereas primary myelofibrosis negative for CALR, JAK2V617F and MPL mutations (so-called triple negative) is associated with a poor prognosis and shorter survival.

The MPL (myeloproliferative leukemia virus oncogene) gene encodes the thrombopoietin receptor, which regulates hematopoiesis and megakaryopoiesis. Activating MPL mutations are associated with a subset of myeloproliferative neoplasms and acute megakaryoblastic leukemia. MPL W515 mutations are present in approximately 5-8% of patients with primary myelofibrosis (PMF) and 1-4% of patients with essential thrombocythemia (ET). The S505 mutation is detected in patients with hereditary thrombocythemia.


Limitations

This assay has a sensitivity of approximately 1% VAF for JAK2V617F and 2.5% VAF for other mutations in JAK2 exons 12 to 15, CALR mutations and MPL mutations. Deletions in CALR up to 70 bp, insertions up to 12 bp, and deletion-insertions (delins) of net length -13 to +11 have been detected in validation studies.

This test was developed and its performance characteristics determined by Labcorp. It has not been cleared or approved by the Food and Drug Administration.

This assay has a sensitivity of approximately 1% VAF for JAK2V617F and 2.5% VAF for other mutations in JAK2 exons 12 to 15, CALR mutations and MPL mutations.

This test was developed and its performance characteristics determined by Labcorp. It has not been cleared or approved by the Food and Drug Administration.

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This test was developed and its performance characteristics determined by Labcorp. It has not been cleared or approved by the Food and Drug Administration.

This assay has a sensitivity of approximately 1% VAF for JAK2V617F and 2.5% VAF for other mutations in JAK2 exons 12 to 15, CALR mutations and MPL mutations. Deletions in CALR up to 70 bp, insertions up to 12 bp, and deletion-insertions (delins) of net length -13 to +11 have been detected in validation studies.

This test was developed and its performance characteristics determined by Labcorp. It has not been cleared or approved by the Food and Drug Administration.


Methodology

Amplicon-based Next Generation Sequencing


References

Alghasham N, Alnouri Y, Abalkhail H, Khalil S. Detection of mutations in JAK2 exons 12-15 by Sanger sequencing. Int J Lab Hematol. 2016 Feb;38(1):34-41.26361084
Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016 May 19;127(20):2391-2405.27069254
Ma W, Kantarjian H, Zhang X, et al. Mutation profile of JAK2 transcripts in patients with chronic myeloproliferative neoplasias. J Mol Diagn. 2009 Jan;11(1):49-53.19074595
NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) Myeloproliferative Neoplasms Version 3.2022 - August 11, 2022.
Swerdlow SH, editor. WHO classification of Tumours of Haematopoietic and Lymphoid Tissues. 4th edn. Lyon, France: International Agency for Research on Cancer; 2017.
Tefferi A. Primary myelofibrosis: 2021 update on diagnosis, risk-stratification and management. Am J Hematol. 2021 Jan;96(1):145-162.33197049
Vainchenker W, Kralovics R. Genetic basis and molecular pathophysiology of classical myeloproliferative neoplasms. Blood. 2017 Feb 9;129(6):667-679.28028029

LOINC® Map

Order Code Order Code Name Order Loinc Result Code Result Code Name UofM Result LOINC
489514 NGS JAK2 E12-15/CALR/MPL 489523 E12-15 Result 48726-4
489514 NGS JAK2 E12-15/CALR/MPL 489524 E12-15 % % N/A
489514 NGS JAK2 E12-15/CALR/MPL 489525 E12-15 Nucleotide 48004-6
489514 NGS JAK2 E12-15/CALR/MPL 489526 E12-15 Amino Acid 48005-3
489514 NGS JAK2 E12-15/CALR/MPL 489515 CALR Result 77174-1
489514 NGS JAK2 E12-15/CALR/MPL 489516 CALR % % N/A
489514 NGS JAK2 E12-15/CALR/MPL 489517 CALR Nucleotide 48004-6
489514 NGS JAK2 E12-15/CALR/MPL 489518 CALR Amino Acid 48005-3
489514 NGS JAK2 E12-15/CALR/MPL 489519 MPL Result 75033-1
489514 NGS JAK2 E12-15/CALR/MPL 489520 MPL % % N/A
489514 NGS JAK2 E12-15/CALR/MPL 489521 MPL Nucleotide 48004-6
489514 NGS JAK2 E12-15/CALR/MPL 489522 MPL Amino Acid 4805-3
489514 NGS JAK2 E12-15/CALR/MPL 489527 E12-15/CALR/MPL Background 62364-5
489514 NGS JAK2 E12-15/CALR/MPL 489528 Method 49549-9
489514 NGS JAK2 E12-15/CALR/MPL 489529 References 75608-0
489514 NGS JAK2 E12-15/CALR/MPL 489530 Director Review 72486-4

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