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CXCR4 Mutation Analysis Test

Last updated July 26, 2019

Approved by: Krish Tangella MD, MBA, FCAP

The CXCR4 Mutation Analysis Blood Test is a genetic test to detect abnormalities in the CXCR4 gene. It aids in the diagnosis of immune deficiency and leukemia (specifically, Waldenström macroglobulinemia).

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

  • C-X-C Chemokine Receptor Type 4 Mutation Analysis Test
  • Leukocyte-Derived Seven Transmembrane Domain Receptor Mutation Analysis Test
  • Neuropeptide Y Receptor Y3 Mutation Analysis Test

What is CXCR4 Mutation Analysis Test? (Background Information)

  • CXCR4 mutation refers to an alteration in the CXCR4 gene, associated with immune deficiency and leukemia (white blood cell cancer)
  • The CXCR4 gene gives instructions for the CXCR3 receptor protein. This protein resides on the membranes of white blood cells and central nervous system cells
  • CXCR4 proteins serve as recognition sites for a specific protein outside the cell: SDF-1 (stromal-derived factor-1). SDF-1 is made in response to infections and other inflammatory events. When it binds to CXCR4 on white blood cells, it exerts 2 main effects:
    • Stimulates growth and division of the cell by turning on signaling pathways that lead to changes in the patterns of conversion of genes to proteins
    • Stimulates migration of the cell towards the bone marrow. The bone marrow contains a high concentration of SDF-1, to which CXCR4-containing cells (such as white blood cells) are attracted. In this way, growing white blood cells gravitate towards the bone marrow, where they finish developing and await release into the bloodstream to fight infection
  • CXCR4 mutation results in a defective CXCR4 receptor that response problematically to SDF-1. Once bound to SDF-1, the altered CXCR4 is unable to let go, prolonging the effects of SDF-1
  • The result of excessive stimulation of CXCR4 by SDF-1 is accumulation of abnormally-developed white blood cells in the bone marrow. This results in immune deficiency, as the individual possesses fewer properly functioning white blood cells than is necessary to fight an infection
  • The CXCR4 Mutation Analysis Blood Test is a genetic test to detect abnormalities in the CXCR4 gene. It aids in the diagnosis of immune deficiency and leukemia (specifically, Waldenström macroglobulinemia)
  • The CXCR4 Mutation Analysis Test also aids in the treatment of leukemia by guiding selection of therapeutic drugs, including disqualifying certain drugs from being used

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 CXCR4 Mutation Analysis Test?

Following are the clinical indications for performing the CXCR4 Mutation Analysis Test:

  • Vision problems, especially blurred or double vision
  • Confusion
  • Dizziness
  • Loss of coordination
  • Headaches
  • Nosebleeds or bleeding gums
  • Fatigue

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 CXCR4 Mutation Analysis Test?

Following is the specimen collection process for CXCR4 Mutation Analysis 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


  • 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 CXCR4 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, 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 CXCR4 Mutation Analysis Test Result?

A mutation in the CXCR4 gene indicates a positive result for the CXCR4 Mutation Analysis Test. This may point to a diagnosis of:

  • Waldenström macroglobulinemia
  • Warts, hypogammaglobulinemia, infections, and myelokathexis syndrome (WHIM syndrome)

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:

  • CXCR4 mutation most notably occurs in a location of the chromosome called 2q22.1 - i.e., the long arm (q) of chromosome 2 in position 22.1.
  • The CXCR4 receptor is one of several receptors used by HIV to infect white blood cells
  • 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.

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


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


References and Information Sources used for the Article:

Helpful Peer-Reviewed Medical Articles:

Reviewed and Approved by a member of the DoveMed Editorial Board
First uploaded: Feb. 1, 2017
Last updated: July 26, 2019