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ABL1 Kinase Domain Mutation Test

Last updated Dec. 16, 2016

The ABL1 Kinase Domain Mutation Test is a genetic test used to guide treatment for chronic myelogenous leukemia.


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

  • Bcr-Abl Kinase Domain Mutation Test

What is ABL1 Kinase Domain Mutation Test? (Background Information)

  • Bcr-Abl mutation refers to a genetic abnormality that makes an individual with chronic myelogenous leukemia (CML) less responsive to treatment
  • Chronic myelogenous leukemia is caused by the inappropriate merging of two genes:
    • The Bcr gene (chromosome 9), which gives instructions for an enzyme called tyrosine kinase; and
    • The Abl gene (chromosome 22)
  • The resulting Bcr-Abl fusion gene leads to overproduction of tyrosine kinase, which causes CML
  • Treatment for CML usually begins with drugs called tyrosine-kinase inhibitors, or TKIs. TKIs are often successful in treating CML
  • However, some individuals may possess a mutation in the Bcr-Abl kinase domain that may contribute to resistance to TKIs and, consequently, relapse
  • The ABL1 Kinase Domain Mutation Test is a genetic test used to guide treatment for chronic myelogenous leukemia. Results of the blood test may aid in the selection of a therapeutic drug or disqualify certain drugs from use

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

  • In situ hybridization technique, such as fluorescence in situ hybridization (FISH)
  • Immunohistochemistry (IHC)
  • Next-generation sequencing (NGS)
  • 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 due to the molecular method 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 ABL1 Kinase Domain Mutation Test?

Following are the clinical indications for performing the ABL1 Kinase Domain Mutation Test: 

  • Monitoring tyrosine-kinase inhibitor therapy
  • Determining the cause for a suboptimal response to first-line treatment using TKIs

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

  • To assist (and in some cases, confirm) the initial diagnosis
  • To distinguish other tumors/conditions that have similar histological features, when examined by a pathologist under the microscope
  • To help in determining treatment options
  • To confirm recurrence of the tumor: Tumor recurrence can either be at the original tumor site, or at a distant location (away from the initial site)

How is the Specimen Collected for ABL1 Kinase Domain Mutation Test?

Following is the specimen collection process for ABL1 Kinase Domain Mutation Test:

The specimen sample requirements may vary from lab to lab. Hence, it is important to contact the testing lab for exact specimen requirements, before initiating the testing process.

  • Sample on which the test is performed may include:
    • Fresh tumor tissue during biopsy
    • Formalin-fixed paraffin-embedded solid tumor tissue (FFPE tumor tissue), often referred to as paraffin block of the tumor
    • Unstained tissue slides
  • Process of obtaining the sample: As outlined by the laboratory testing facility
  • Preparation required: As outlined by the laboratory testing facility

Note:

  • In some cases, a different source of specimen (such as peripheral blood, bone marrow biopsy specimen, or other body fluids) 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
  • Depending on the location of testing, it may take up to 2 weeks’ turnaround time, to obtain the test results
  • 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 tumor specimen over time

Cost of ABL1 Kinase Domain Mutation 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, out-of-network and in-network of your healthcare providers and healthcare facilities
  • 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 that is necessary (if any)

What is the Significance of the ABL1 Kinase Domain Mutation Test Result?

  • A positive value for the ABL1 Kinase Domain Mutation Test may indicate certain tyrosine-kinase inhibitors are not appropriate to use in an individual with chronic myelogenous leukemia. Consequently, alternative options may be necessary

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:

  • The most commonly used TKI is imatinib. Others include lapatinib, nilotinib, and sorafenib
  • Imatinib gained FDA approval in 2001. Previously, only highly toxic drugs, such as busulfan and hydroxyurea, were used
  • Many laboratories may not have the capability to perform this test. Only highly-specialized labs with advanced facilities and testing procedures may perform 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 of 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/common-procedures/procedures-laboratory/bcr-abl-test/

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)

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Reviewed and Approved by a member of the DoveMed Editorial Board
First uploaded: Dec. 16, 2016
Last updated: Dec. 16, 2016