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
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.
For more information the following algorithms are available:
-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.
Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test
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.
For more information the following algorithms are available:
-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: Whole 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 whole blood specimen in original tube. Do not aliquot.
3. Label specimen as blood.
Specimen Stability Information: Ambient (preferred)/Refrigerate 7 days
Specimen Type: Bone marrow
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 bone marrow specimen in original tube. Do not aliquot.
3. Label specimen as bone marrow.
Specimen Stability Information: Ambient (preferred)/Refrigerate 7 days
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. The minimum volume is sufficient for one attempt at testing.
Blood, bone marrow: 0.5 mL; Extracted DNA: 50 mcL at 20 ng/mcL concentration
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.
For more information the following algorithms are available:
-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
The JAK2 V617F variant is present in 95% to 98% of patients with polycythemia vera , 50% to 60% of patients with primary myelofibrosis (PMF), and 50% to 60% of patients with 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 patients with PMF. 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(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. 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
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. 2014;28(7):1472-1477
5. Pikman Y, Lee BH, Mercher T, et al. MPLW515L is a novel somatic activating mutation in myelofibrosis with myeloid metaplasia. PLoS Med. 2006;3(7):e270
6. Pardanani AD, Levine RL, Lasho T, et al. MPL515 mutations in myeloproliferative and other myeloid disorders: a study of 1182 patients. Blood. 2006;108(10):3472-3476
7. Defour JP, Chachoua I, Pecquet C, Constantinescu SN. Oncogenic activation of MPL/thrombopoietin receptor by 17 mutations at W515: implications for myeloproliferative neoplasms. Leukemia. 2016;30(5):1214-1216. doi:10.1038/leu.2015.271
Method Description
Describes how the test is performed and provides a method-specific reference
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 unaltered CALR will show an amplicon at 266 base pairs (bp), an altered CALR with insertion will show an amplicon greater than 266 bp, and an altered 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%.(Unpublished Mayo method)
Genomic DNA is extracted, and Sanger sequencing is used to evaluate for variants in MPL, exon 10. The sensitivity of this assay is approximately 20%, such that samples containing lower percentages of altered DNA will appear negative.(Unpublished Mayo method)
PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information
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.
Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded
Performing Laboratory Location
Indicates the location of the laboratory that performs the test
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.
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 |