TEST CATALOG ORDERING & RESULTS SPECIMEN HANDLING CUSTOMER SERVICE EDUCATION & INSIGHTS
Test Catalog

Test ID: MPNCM    
Myeloproliferative Neoplasm, CALR with Reflex to MPL, Varies

Useful For Suggests clinical disorders or settings where the test may be helpful

Aiding in the distinction between a reactive cytosis and a myeloproliferative neoplasm when JAK2V617F testing result is negative

Testing Algorithm Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

This test reflexively evaluates for variants in the CALR and MPL genes commonly associated with BCR/ABL1-negative myeloproliferative neoplasms. The testing sequence is based on the reported frequency of gene variants in this disease group. It is usually ordered when a JAK2 V617F result is known to be negative. Initial testing evaluates for the presence of the CALR insertions and deletions. If out-of-frame CALR insertions or deletions are detected, the testing algorithm ends. If the CALR result is negative or an in-frame CALR insertion or deletion is identified, then testing proceeds, at an additional charge, to evaluate for variants in exon 10 of the MPL gene by Sanger sequencing. An integrated report is issued with the summary of test results.

 

The following algorithms are available in Special Instructions:

-Myeloproliferative Neoplasm: A Diagnostic Approach to Bone Marrow Evaluation

-Myeloproliferative Neoplasm: A Diagnostic Approach to Peripheral Blood Evaluation

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

JAK2 V617F variant is present in 95% to 98% of polycythemia vera (PV) patients, 50% to 60% of primary myelofibrosis (PMF) patients, and 50% to 60% of essential thrombocythemia (ET) patients. Detection of the JAK2 V617F variant helps establish the diagnosis of a myeloproliferative neoplasm (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 variants (20%-30% of PMF and ET) and MPL exon 10 variants (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 Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

An interpretive report will be provided.

Interpretation Provides information to assist in interpretation of the test results

The results will be reported as 1 of the 3 following states:

-Positive for CALR variant

-Positive for MPL variant

-Negative for CALR and MPL variants

 

Positive variants status is highly suggestive of a myeloid neoplasm and clinicopathologic correlation is necessary in all cases.

 

Negative variant status does not exclude the presence of a myeloproliferative neoplasm or other neoplasms.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

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.

Clinical Reference Recommendations for in-depth reading of a clinical nature

1. Klampfl T, Gisslinger H, Harutyunyan AS, et al: Somatic mutation of calreticulin in myeloproliferative neoplasms. N Engl J Med 2013;369:2379-2390

2. Nangalia J, Massie CE, Baxter EJ, et al: Somatic CALR mutation in myeloproliferative neoplasms with nonmutated JAK2. N Engl J Med 2013;369:2391-2405

3. Rotunno G, Mannarelli C, Guglielmelli P, et al: Impact of calreticulin mutations on clinical and hematological phenotype and outcome in essential thrombocythemia. Blood 2014;123:1552-1555

4. Tefferi A, Lasho TL, Finke CM, et al: CALR vs JAK2 vs MPL-mutated or triple-negative myelofibrosis: clinical, cytogenetic and molecular comparisons. Leukemia advance online publication 21 January 2014

5. Pikman Y, Lee BH, Mercher T, et al: MPLW515L is a novel somatic activating mutation in myelofibrosis with myeloid metaplasia. FLoS Med 2006;3:e270

6. Pardanani A, Levine R, Lasho T, et al: MPL515 mutations in myeloproliferative and other myeloid disorders: a study of 1182 patients. Blood 2006;15:3472

Special Instructions Library of PDFs including pertinent information and forms related to the test