JAK2V617F Mutation Analysis, Qualitative, with Reflex to CALR Mutation Analysis, JAK2 Exon 12-15 Mutation Analysis and MPL Mutation Analysis

CPT: 81270
Print Share

Test Details

Synonyms

  • CALR Mutation Analysis
  • JAK2 Exon 12-15 Mutation Detection
  • Janus Kinase 2 V617F Mutation Detection
  • MPL Mutation Analysis

Use

This test will assess for the JAK2V617F (exon 14) mutation first and will reflex to CALR mutation analysis, JAK2 exon 12 to 15 mutation analysis and MPL mutation analysis when the JAK2V617F mutation is negative.

Limitations

This assay has a sensitivity of approximately 1% for the detection of cells containing the JAK2 mutations and 15% for JAK2 exon 12 to 15 and 5% for CALR mutations, 10% to 20% for MPL mutations in a background of non-mutant cells.

This test was developed, and its performance characteristics determined, by LabCorp. It has not been cleared or approved by the US Food and Drug Administration (FDA).

Methodology

Polymerase chain reaction (PCR); capillary electrophoresis; Sanger sequencing

Additional Information

The JAK2V617F (exon 14) mutation analysis can be used in conjunction with bone marrow histology and cytogenetic analysis to assist in the diagnosis of myeloproliferative neoplasms (MPN). The JAK2V617F mutation is found in almost all patients with polycythemia vera (PV) and in nearly one-half of those with idiopathic myelofibrosis (IMF) and with essential thrombocythemia (ET). A small percentage (~3.3%) of JAK2 mutation positive patients contain other non-V617F mutation with exon 12 to 15.

The calcium-binding endoplasmic reticulin chaperone protein, calreticulin (CALR), is somatically mutated in approximately 70% of patients with JAK2-negative essential thrombocythemia (ET) and 60% to 88% of patients with JAK2-negative primary myelofibrosis. Only a minority of patients (approximately 8%) with myelodysplasia has mutations in 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 appear to be mutually exclusive with JAK2 mutations and MPL mutations.

MPL (myeloproliferative leukemia virus oncogene homology) belongs to the hematopoietin superfamily and enables its ligand thrombopoietin, to facilitate both global hematopoiesis and megakaryocyte growth and differentiation. MPL W515 mutations are present in patients with primary myelofibrosis (PMF) and essential thrombocythemia (ET) at a frequency of approximately 5% and 1%, respectively. The S505 mutation is detected in patients with hereditary thrombocythemia.

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 or green-top (sodium heparin) 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

Refrigerate. Ship specimen at room temperature. Specimen should arrive in the laboratory within 48 hours of collection. If specimen is to be stored prior to shipment, store at 2°C to 8°C. Indicate date and time of collection on the test request form.

Causes for Rejection

Sample more than 72 hours old; frozen whole blood, serum or bone marrow; leaking tube; clotted blood or bone marrow; grossly hemolyzed specimen or otherwise visibly degraded or unsuitable; specimens containing suspicious foreign material

Clinical Information

Special Instructions

Please direct any questions regarding this test to customer service at 800-345-4363.

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
Baxter EJ, Scott LM, Campbell PJ, et al. Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet. 2005 Mar 19-25;365(9464):1054-1061.15781101
James C, Ugo V, LeCoudéic JP, et al. A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera. Nature. 2005 Apr 28;434(7037):1144-1148.15793561
Jones AV, Kreil S, Zoi K, et al. Widespread occurrence of the JAK2V617F mutation in chronic myeloproliferative disorders. Blood. 2005 Sep 15;106(6):2162-2168.15920007
Kilpivaara O, Levine RL. JAK2 and MPL mutations in myeloproliferative neoplasms: Discovery and science. Leukemia. 2008 Oct;22(10):1813-1817.18754026
Klampfl T, Gisslinger H, Harutyunyan AS, et al. Somatic mutations of calreticulin in myeloproliferative neoplasms. N Engl J Med. 2013 Dec 19;369(25):2379-2390.24325356
Kralovics R, Passamonti F, Buser AS, et al. A gain-of-function mutation of JAK2 in myeloproliferative disorders. N Engl J Med. 2005 Apr 28;352(17):1779-1790.15858187
Liu K, Martini M, Rocca B, et al. Evidence for a founder effect of the MPL-S505N mutation in eight Italian pedigrees with hereditary thrombocythemia. Haematologica. 2009 Oct;94(10):1368-1374.19608689
Ma W, Kantarjian H, Zhang X, et al. Mutation profile of JAK2 transcripts in patients with chronic myeloproliferative meoplasias. J Mol Diagn. 2009 Jan;11(1):49-53.19074595
Nangalia J, Massie CE, Baxter EJ, et al. Somatic CALR mutations in myeloproliferative neoplasms with nonmutated JAK2. N Engl J Med. 2013 Dec;369(25):2391-2405.24325359
Pardanani AD, Levine RL, Lasho T, et al. MPL515 mutations in myeloproliferative and other myeloid disorders: A study of 1182 patients. Blood. 2006 Nov 15;108(10):3472-3476.16868251
Tefferi A, Gilliland DG. The JAK2V617F tyrosine kinase mutation in myeloproliferative disorders: status report and immediate implications for disease classification and diagnosis. Mayo Clin Proc. 2005 Jul;80(7):947-958.16007902

LOINC® Map

Order Code Order Code Name Order Loinc Result Code Result Code Name UofM Result LOINC
489421 JAK2 V617F Rfx CALR/E12-15/MPL 489201 JAK2 V617F mutation detection 43399-5
489421 JAK2 V617F Rfx CALR/E12-15/MPL 489347 Background: 77202-0
489421 JAK2 V617F Rfx CALR/E12-15/MPL 489204 Director Review: 72486-4
489421 JAK2 V617F Rfx CALR/E12-15/MPL 489419 Reflex: N/A
489421 JAK2 V617F Rfx CALR/E12-15/MPL 489355 Extraction N/A
489421 JAK2 V617F Rfx CALR/E12-15/MPL 489457 JAK2 Mutation Analysis, Qual N/A
Reflex Table for Reflex:
Order Code Order Name Result Code Result Name UofM Result LOINC
Reflex 1 489425 CALR+JAK2 E12-15+MPL 489451 CALR Mutation Detection Result 77174-1
Reflex Table for Reflex:
Order Code Order Name Result Code Result Name UofM Result LOINC
Reflex 1 489425 CALR+JAK2 E12-15+MPL 489461 Background: N/A
Reflex Table for Reflex:
Order Code Order Name Result Code Result Name UofM Result LOINC
Reflex 1 489425 CALR+JAK2 E12-15+MPL 489453 Methodology: 49549-9
Reflex Table for Reflex:
Order Code Order Name Result Code Result Name UofM Result LOINC
Reflex 1 489425 CALR+JAK2 E12-15+MPL 489454 References: 75608-0
Reflex Table for Reflex:
Order Code Order Name Result Code Result Name UofM Result LOINC
Reflex 1 489425 CALR+JAK2 E12-15+MPL 489449 Director Review: 72486-4
Reflex Table for Reflex:
Order Code Order Name Result Code Result Name UofM Result LOINC
Reflex 1 489425 CALR+JAK2 E12-15+MPL 115328 JAK2 Exons 12-15 Mut Det PCR 48726-4
Reflex Table for Reflex:
Order Code Order Name Result Code Result Name UofM Result LOINC
Reflex 1 489425 CALR+JAK2 E12-15+MPL 489415 Indications 42349-1
Reflex Table for Reflex:
Order Code Order Name Result Code Result Name UofM Result LOINC
Reflex 1 489425 CALR+JAK2 E12-15+MPL 489416 Specimen Type 31208-2
Reflex Table for Reflex:
Order Code Order Name Result Code Result Name UofM Result LOINC
Reflex 1 489425 CALR+JAK2 E12-15+MPL 489391 Nucleotide Change 48004-6
Reflex Table for Reflex:
Order Code Order Name Result Code Result Name UofM Result LOINC
Reflex 1 489425 CALR+JAK2 E12-15+MPL 489392 Amino Acid Change 48005-3
Reflex Table for Reflex:
Order Code Order Name Result Code Result Name UofM Result LOINC
Reflex 1 489425 CALR+JAK2 E12-15+MPL 489393 Background 77202-0
Reflex Table for Reflex:
Order Code Order Name Result Code Result Name UofM Result LOINC
Reflex 1 489425 CALR+JAK2 E12-15+MPL 489394 Method 49549-9
Reflex Table for Reflex:
Order Code Order Name Result Code Result Name UofM Result LOINC
Reflex 1 489425 CALR+JAK2 E12-15+MPL 489412 References 75608-0
Reflex Table for Reflex:
Order Code Order Name Result Code Result Name UofM Result LOINC
Reflex 1 489425 CALR+JAK2 E12-15+MPL 489413 Director Review 72486-4
Reflex Table for Reflex:
Order Code Order Name Result Code Result Name UofM Result LOINC
Reflex 1 489425 CALR+JAK2 E12-15+MPL 489377 MPL Mutation Analysis Result: 62947-7
Reflex Table for Reflex:
Order Code Order Name Result Code Result Name UofM Result LOINC
Reflex 1 489425 CALR+JAK2 E12-15+MPL 489152 Nucleotide Change: 48004-6
Reflex Table for Reflex:
Order Code Order Name Result Code Result Name UofM Result LOINC
Reflex 1 489425 CALR+JAK2 E12-15+MPL 489154 Amino Acid Change: 48005-3
Reflex Table for Reflex:
Order Code Order Name Result Code Result Name UofM Result LOINC
Reflex 1 489425 CALR+JAK2 E12-15+MPL 489155 Background: 8251-1
Reflex Table for Reflex:
Order Code Order Name Result Code Result Name UofM Result LOINC
Reflex 1 489425 CALR+JAK2 E12-15+MPL 489167 Methodology: 62948-5
Reflex Table for Reflex:
Order Code Order Name Result Code Result Name UofM Result LOINC
Reflex 1 489425 CALR+JAK2 E12-15+MPL 489157 References: 75608-0
Reflex Table for Reflex:
Order Code Order Name Result Code Result Name UofM Result LOINC
Reflex 1 489425 CALR+JAK2 E12-15+MPL 489158 Director Review: 72486-4

For Providers

Please login to order a test.

 

© 2017  Laboratory Corporation of America® Holdings and Lexi-Comp Inc. All Rights Reserved.

CPT Statement/Profile Statement

The LOINC® codes are copyright © 1994-2017, Regenstrief Institute, Inc. and the Logical Observation Identifiers Names and Codes (LOINC) Committee. Permission is granted in perpetuity, without payment of license fees or royalties, to use, copy, or distribute the LOINC® codes for any commercial or non-commercial purpose, subject to the terms under the license agreement found at https://loinc.org/license/. Additional information regarding LOINC® codes can be found at LOINC.org, including the LOINC Manual, which can be downloaded at LOINC.org/downloads/files/LOINCManual.pdf