Test Catalog

Test Id : MPNCM

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Myeloproliferative Neoplasm, CALR with Reflex to MPL, Varies

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Overview

Test Catalog

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

Reflex Tests
Lists tests that may or may not be performed, at an additional charge, depending on the result and interpretation of the initial tests.

Test Id Reporting Name Available Separately Always Performed
MPNML MPL Exon 10 Sequencing, Reflex No, (bill only) No

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

Method Name
A short description of the method used to perform the test

Polymerase Chain Reaction (PCR) and Fragment Analysis

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.

Yes

Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

MPN (CALR, MPL) Reflex

Aliases
Lists additional common names for a test, as an aid in searching

CALR

Essential Thrombocythemia

JAK2-negative Myeloproliferative Neoplasm

Janus kinase 2 gene

MPL S505

MPL W515

Myelofibrosis

Myeloproliferative Disorder

Myeloproliferative leukemia virus oncogene

Myeloproliferative Neoplasm (MPN)

Primary Myelofibrosis

Tyrosine Kinase Mutation

Calreticulin

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

Specimen Type
Describes the specimen type validated for testing

Varies

Shipping Instructions

Specimen must arrive within 7 days of collection.

Necessary Information

The following information is required:

1. Pertinent clinical history

2. Clinical or morphologic suspicion

3. Date of collection

4. Specimen source

ORDER QUESTIONS AND ANSWERS

Question ID Description Answers
MP036 Specimen Type

Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

Submit only 1 of the following specimens:

 

Specimen Type: Blood

Container/Tube: Lavender top (EDTA) or yellow top (ACD-B)

Specimen Volume: 3 mL

Collection Instructions:

1. Invert several times to mix blood.

2. Send specimen in original tube.

3. Label specimen as blood.

Specimen Stability Information: Ambient (preferred)/Refrigerate

 

Specimen Type: Bone marrow aspirate

Container/Tube: Lavender top (EDTA) or yellow top (ACD-B)

Specimen Volume: 2 mL

Collection Instructions:

1. Invert several times to mix specimen.

2. Send specimen in original tube.

3. Label specimen as bone marrow.

Specimen Stability Information: Ambient (preferred)/Refrigerate

 

Specimen Type: Extracted DNA from blood or bone marrow

Container/Tube: 1.5 to 2 mL tube

Specimen Volume: Entire specimen

Collection Instructions:

1. Indicate volume and concentration of DNA

2. Label specimen as extracted DNA from blood or bone marrow.

Specimen Stability Information: Frozen (preferred)/Refrigerate/Ambient

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

Forms

If not ordering electronically, complete, print, and send a Hematopathology/Cytogenetics Test Request (T726) with the specimen.

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the Testing Laboratory

Blood or Bone marrow: 0.5 mL

Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected

Gross hemolysis Reject
Paraffin-embedded bone marrow aspirate clot or biopsy blocks Slides Paraffin shavings Moderately to severely clotted Reject

Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included

Specimen Type Temperature Time Special Container
Varies Varies 7 days

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

Method Description
Describes how the test is performed and provides a method-specific reference

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 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 variant-containing cells in 100 total cells) in most variant types, except for the rare type of 1-bp deletion, which has a sensitivity of approximately 20%. This is a laboratory developed test using analyte-specific reagents and research use only (RUO) reagents.(Unpublished Mayo method)

 

Genomic DNA is extracted and Sanger sequencing used to evaluate for variants in MPL, exon 10. The sensitivity of this assay is approximately 20%, such that samples containing lower percentages of mutated DNA will appear negative.(Unpublished Mayo method)

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information

No

Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.

Monday through Friday

Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.

7 to 10 days

Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

DNA: 3 months

Performing Laboratory Location
Indicates the location of the laboratory that performs the test

Rochester

Fees
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.

  • Authorized users can sign in to Test Prices for detailed fee information.
  • Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
  • Prospective clients should contact their account representative. For assistance, contact Customer Service.

Test Classification
Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.

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
Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

CPT codes are provided by the performing laboratory.

81219-CALR (calreticulin) (eg, myeloproliferative disorders), gene analysis, common variants in exon 9

81339 -MPL (MPL proto-oncogene, thrombopoietin receptor) (eg, myeloproliferative disorder) gene analysis; sequence analysis, exon 10 (if appropriate)

LOINC® Information
Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and results codes of this test. LOINC values are provided by the performing laboratory.

Test Id Test Order Name Order LOINC Value
MPNCM MPN (CALR, MPL) Reflex In Process
Result Id Test Result Name Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
42393 MPNCM Reflex Result 82939-0
MP036 Specimen Type 31208-2
42392 Final Diagnosis 50398-7

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

Excel | PHP Pdf | CMS Pdf

Sample Reports
Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports
International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports