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MPL Mutation Analysis Test

Last updated May 29, 2017

Approved by: Krish Tangella MD, MBA, FCAP

The MPL Mutation Analysis Test is a genetic test that detects abnormalities in the MPL gene. It is used to diagnose megakaryocytopenia and thrombocytopenia, among other blood cell deficiencies.


What are other Names for this Test? (Equivalent Terms)

  • CD110 Mutation Analysis Test
  • Myeloproliferative Leukemia Virus Oncogene Mutation Analysis Test
  • Thrombopoietin Receptor Precursor Mutation Analysis Test

What is MPL Mutation Analysis Test? (Background Information)

  • MPL mutation refers to an alteration in the MPL gene, which is associated with clotting disorders such as essential thrombocytopenia
  • The MPL gene gives instructions for a protein called thrombopoietin receptor (TR). TR is important for communication between cells
  • TR is present on the membranes of early blood cells. It acts as an antenna that relays signals from outside the cell to inside the cell, and influences growth and division
  • The signal recognized by TR is a protein called thrombopoietin. TR then activates a chain of events inside the cell mediated by a signal transmission pathway called the JAK/STAT pathway
  • The final result of activation of TR by thrombopoietin is increased growth and division of the cell. In the case of developing cells, such as blood cells, this process is essential to the formation of white blood cells, red blood cells, and platelets
  • TR also plays a role in platelet production. Platelets are made from large cells called megakaryocytes. In fact, platelets are not technical cells, but fragments of megakaryocytes
  • Alterations in the MPL gene may result in a TR protein that is unable to recognize thrombopoietin and create healthy blood cells. Individuals with mutation MPL often exhibit low levels of platelets, and thus, their ability to stop bleeding and form blood clots is impaired
  • The MPL Mutation Analysis Test is a genetic test that detects abnormalities in the MPL gene. It is used to diagnose megakaryocytopenia and thrombocytopenia, among other blood cell deficiencies
  • The MPL Mutation Analysis Test also aids in the treatment of blood cell disorders by guiding selection of therapeutic drugs, including disqualifying certain drugs from use

Molecular testing, in general, can be performed using a variety of methods. Some of these methods include:

  • In situ hybridization techniques, such as fluorescence in situ hybridization (FISH)
  • Immunohistochemistry (IHC)
  • Next-generation sequencing (NGS)
  • Methylation profiling
  • Polymerase chain reaction (PCR)
  • Comparative genomic hybridization (CGH)
  • Karyotyping including spectral karyotyping
  • mRNA analysis
  • Tissue microarrays (TMAs)
  • Southern blot test
  • Northern blot test
  • Western blot test
  • Eastern blot test

The methodology used for the test may vary from one laboratory to another.

Note: Molecular testing has limitations depending on the method being used, and genetic mutational abnormalities being tested. This can affect the results on a case-by-case basis. Consultation with your healthcare provider will help in determining the right test and right molecular method, based on individual circumstances.

What are the Clinical Indications for performing the MPL Mutation Analysis Test?

Following are the clinical indications for performing the MPL Mutation Analysis Test: 

  • Easy or excessive bruising (purpura)
  • Superficial bleeding into the skin that appears as a rash of pinpoint-sized reddish-purple spots (petechiae), usually on the lower legs
  • Prolonged bleeding from cuts
  • Bleeding from your gums or nose
  • Blood in urine or stools
  • Unusually heavy menstrual flows
  • Fatigue
  • Enlarged spleen
  • Jaundice

In general, the molecular genetic testing is undertaken in the following situations: 

  • To assist (and in some cases, confirm) the initial diagnosis
  • To check for or ascertain a family history of the condition
  • To distinguish other conditions that have similar features (signs and symptoms)
  • To help determine treatment options

How is the Specimen Collected for MPL Mutation Analysis Test?

The type and source and specimen sample requirements will depend on the preference of the individuals and the preference of the testing lab. Thus, it may vary from one individual to another and from one lab to another. Therefore, it is important to contact the testing lab for exact specimen requirements, before initiating the collecting and testing process.

Following is the specimen collection process for MPL Mutation Analysis Test:

  • Sample on which the test is performed may include:
    • Peripheral blood in individuals showing signs and symptoms suspected of the condition
    • Bone marrow biopsy specimen
    • For mitochondrial DNA testing, usually a muscle biopsy or a liver biopsy is preferred
    • In case of expectant mothers, prenatal testing through amniotic fluid and chorionic villi sampling
    • Fetal cord blood
    • Fresh tissue from biopsy
    • Fresh tissue from autopsy sample
    • Fresh tissue from fetal demise
    • Buccal brushes: Using the kit that is provided by the testing laboratory, buccal brushes can be used to collect the specimen, by scraping the inner cheek lining (buccal mucosa)
    • Oral rinse specimens
    • Body fluids such as saliva, tears, and semen
    • Dried blood spots: This specimen type is usually requested in situations where the collection and/or shipping of whole blood is not practical
    • In some cases, hair samples (with attached roots), finger nails, and buccal swabs, may be acceptable
    • Formalin-fixed paraffin-embedded solid tumor tissue (FFPE tumor tissue), often referred to as paraffin block of the tumor
    • Products of conception sample from aborted pregnancy
  • Process of obtaining the sample: As outlined by the laboratory testing facility
  • Preparation required: As outlined by the laboratory testing facility

Important information:

Limitations of specimen while testing for the condition

  • For blood specimens: Individuals, who have received platelet transfusions, red blood transfusion, or white blood (leukocyte) transfusion, should wait at least 4 weeks before providing a blood specimen
  • The following specimens may not be acceptable in individuals who have received heterologous bone marrow transplant (in the past):
    • Peripheral blood samples
    • Oral rinse specimens
    • Bone marrow biopsy specimens
  • Testing should not be performed on a transplanted organ/specimen, since the genetic material belongs to the donor and not to the individual being tested
  • Formalin-fixed paraffin-embedded solid tumor tissue: In many cases, FFPE tissue blocks are usually not acceptable. Please contact the testing lab to ascertain, if it is an acceptable sample specimen
  • In some cases, a different source of specimen may be acceptable to the laboratory performing the test

Occasionally, additional samples may be required to either repeat the test or to perform follow-up testing.

Turnaround time for test results

  • Depending on the location of testing, it may take from 2 to 8 weeks from the time of sample collection, to obtain the test results

Sample storage information

  • Many hospitals preserve the paraffin blocks for at least 7 years
  • In general, older paraffin blocks (over 5 years) may affect the detection of specific mutations, due to degradation of the tissue specimen over time

Cost of MPL Mutation Analysis Test:

  • The cost of the test procedure depends on a variety of factors, such as the type of your health insurance, annual deductibles, co-pay requirements, whether your healthcare provider/facility is in-network or out-of-network of your insurance company
  • In many cases, an estimate may be provided before the test is conducted. The final amount may depend upon the findings during the test procedure and post-operative care, if required

What is the Significance of the MPL Mutation Analysis Test Result?

A mutation in the MPL gene indicates a positive result for the MPL Mutation Analysis Test. This may point to a diagnosis of any of the following:

  • Congenital amegakaryocytic thrombocytopenia (CAMT)
  • Essential thrombocytopenia
  • Primary myelofibrosis

The laboratory test results are NOT to be interpreted as results of a "stand-alone" test. The test results have to be interpreted after correlating with suitable clinical findings and additional supplemental tests/information. Your healthcare providers will explain the meaning of your tests results, based on the overall clinical scenario.

Additional and Relevant Useful Information:

  • MPL mutation most notably occurs in a location of the chromosome called 1p34.2 i.e., the short arm (p) of chromosome 1 in position 34.2
  • Many laboratories may not have the capability to perform this test. Only highly-specialized labs with advanced facilities and testing procedures may offer this test

Certain medications that you may be currently taking may influence the outcome of the test. Hence, it is important to inform your healthcare provider, the complete list of medications (including any herbal supplements) you are currently taking. This will help the healthcare provider interpret your test results more accurately and avoid unnecessary chances of a misdiagnosis.

What are some Useful Resources for Additional Information?

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/primary-myelofibrosis/

Please visit our Laboratory Procedures Center for more physician-approved health information:

http://www.dovemed.com/common-procedures/procedures-laboratory/

References and Information Sources used for the Article:

https://ghr.nlm.nih.gov/primer/testing/genetictesting (accessed on 05/10/2017)

https://www.cdc.gov/mmwr/preview/mmwrhtml/rr5806a1.htm (accessed on 05/10/2017)

http://www.nature.com/gim/journal/v10/n5/full/gim200852a.html (accessed on 05/10/2017)

http://pediatrics.aappublications.org/content/106/6/1494 (accessed on 05/10/2017)

MPL gene - Genetics Home Reference. (n.d.). Retrieved from https://ghr.nlm.nih.gov/gene/MPL#location

Thrombocytopenia (low platelet count) Symptoms - Mayo Clinic. (2015, March 31). Retrieved from http://www.mayoclinic.org/diseases-conditions/thrombocytopenia/basics/symptoms/con-20027170

Helpful Peer-Reviewed Medical Articles:

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Drets, M. E., & Shaw, M. W. Specific banding patterns of human chromosomes. Proceedings of the National Academy of Sciences 68, 2073–2077 (1971)

Druker, B. J. Perspectives on the development of a molecularly targeted agent. Cancer Cell 1, 31–36 (2002)

Parra, I., & Windle, B. High resolution visual mapping of stretched DNA by fluorescent hybridization. Nature Genetics 5, 17–21 (1993) doi:10.1038/ng0993-17

Pinkel, D., et al. High resolution analysis of DNA copy number variation using comparative genomic hybridization to microarrays. Nature Genetics 20, 207–211 (1998) doi:10.1038/2524

Speicher, M. R., et al. Karyotyping human chromosomes by combinatorial multi-fluor FISH. Nature Genetics 12, 368–375 (1996) doi:10.1038/ng0496-368

Brecqueville, M., Rey, J., Bertucci, F., Coppin, E., Finetti, P., Carbuccia, N., ... & Verrot, D. (2012). Mutation analysis of ASXL1, CBL, DNMT3A, IDH1, IDH2, JAK2, MPL, NF1, SF3B1, SUZ12, and TET2 in myeloproliferative neoplasms. Genes, Chromosomes and Cancer, 51(8), 743-755.

Ma, W., Zhang, X., Wang, X., Zhang, Z., Yeh, C. H., Uyeji, J., & Albitar, M. (2011). MPL mutation profile in JAK2 mutation-negative patients with myeloproliferative disorders. Diagnostic Molecular Pathology, 20(1), 34-39.

Jones, A. V., Campbell, P. J., Beer, P. A., Schnittger, S., Vannucchi, A. M., Zoi, K., ... & Silver, R. T. (2010). The JAK2 46/1 haplotype predisposes to MPL-mutated myeloproliferative neoplasms. Blood, 115(22), 4517-4523.

Tefferi, A., Lasho, T. L., Abdel-Wahab, O., Guglielmelli, P., Patel, J., Caramazza, D., ... & Mai, M. (2010). IDH1 and IDH2 mutation studies in 1473 patients with chronic-, fibrotic-or blast-phase essential thrombocythemia, polycythemia vera or myelofibrosis. Leukemia, 24(7), 1302-1309.

Boyd, E. M., Bench, A. J., Goday‐Fernández, A., Anand, S., Vaghela, K. J., Beer, P., ... & Erber, W. N. (2010). Clinical utility of routine MPL exon 10 analysis in the diagnosis of essential thrombocythaemia and primary myelofibrosis. British journal of haematology, 149(2), 250-257.

Tefferi, A., Noel, P., & Hanson, C. A. (2011). Uses and abuses of JAK2 and MPL mutation tests in myeloproliferative neoplasms: a paper from the 2010 William Beaumont Hospital Symposium on Molecular Pathology. The Journal of Molecular Diagnostics, 13(5), 461-466.

Reviewed and Approved by a member of the DoveMed Editorial Board
First uploaded: May 29, 2017
Last updated: May 29, 2017