BCR-ABL Test – Meaning, Procedure, Normal Range & Results

What is the BCR-ABL Gene?

The BCR-ABL gene is an abnormal fusion gene that forms when a part of the BCR gene on chromosome 22 joins with a part of the ABL gene on chromosome 9.
This genetic mistake leads to the creation of a new, combined chromosome known as the Philadelphia chromosome.

Because of this fusion, an abnormal enzyme called tyrosine kinase is produced. This enzyme continuously sends signals that tell the bone marrow to produce too many white blood cells, which is a hallmark of certain blood cancers, especially Chronic Myeloid Leukemia (CML) and some cases of Acute Lymphoblastic Leukemia (ALL).

The BCR-ABL test detects the presence and amount of this fusion gene in the blood or bone marrow. It helps in diagnosing, monitoring, and managing these cancers effectively.

Where is BCR-ABL Formed in the Body?

The BCR-ABL gene is not inherited from parents. It develops during a person’s lifetime due to a random mutation in the bone marrow stem cells, which are responsible for producing blood cells.

This happens because of a process called reciprocal translocation, where parts of two different chromosomes (chromosome 9 and 22) swap places. When this happens, the new fusion gene (BCR-ABL) forms and begins producing abnormal signals that drive uncontrolled cell division.

Purpose and Importance of the BCR-ABL Test

The BCR-ABL test plays a vital role in leukemia management. It helps doctors make key decisions regarding diagnosis, treatment, and follow-up care.

1. Diagnosis

The test confirms the presence of the Philadelphia chromosome, which is a defining feature of:

• Chronic Myeloid Leukemia (CML)
• Philadelphia-positive Acute Lymphoblastic Leukemia (Ph+ ALL)

A positive BCR-ABL result helps confirm the type of leukemia and guides the treatment plan.

2. Treatment Guidance

The test results help determine if the patient will benefit from targeted therapy using tyrosine kinase inhibitors (TKIs) such as:

• Imatinib (Gleevec)
• Dasatinib
• Nilotinib
• Bosutinib
• Ponatinib

These medicines specifically block the abnormal BCR-ABL tyrosine kinase enzyme, helping control cancer growth.

3. Monitoring Treatment Effectiveness

After starting therapy, the BCR-ABL test is used regularly to:

• Measure how much the fusion gene level has decreased.
• Monitor if the treatment is working.
• Detect early signs of relapse or treatment resistance.

If the BCR-ABL level keeps falling, it means the treatment is effective. If the level starts rising again, it may suggest a possible relapse.

Causes of Low or Negative BCR-ABL Levels

A low or negative test result is generally a good sign. It means there is no active disease or that the cancer is well controlled.

Common reasons include:

• No presence of the BCR-ABL fusion gene (normal healthy result)
• Successful treatment, where leukemia cells have been destroyed
• Molecular remission, meaning the fusion gene is undetectable at the molecular level
• Early-stage disease, where the number of abnormal cells is too low for the test to detect

Symptoms of Low or Negative BCR-ABL Levels

There are usually no symptoms related to a negative BCR-ABL result. In fact, it is a positive outcome.

If the patient is already under treatment, a low or negative result indicates:

• The therapy is working effectively.
• The body is returning to normal blood cell production.
• The person may be entering remission, where the cancer shows no active signs.

Causes of High or Positive BCR-ABL Levels

A positive or high BCR-ABL result means the fusion gene is present in the blood or bone marrow. This suggests that leukemia cells are still active or have returned.

Common reasons include:

• Presence of BCR-ABL mutation in bone marrow cells
• Active or relapsed leukemia (CML or Ph+ ALL)
• Partial response to therapy, where some abnormal cells remain
• Resistance to tyrosine kinase inhibitor drugs

Symptoms of High or Positive BCR-ABL Levels

The symptoms are related to the underlying leukemia, not the test itself. Common signs include:

• Persistent fatigue or weakness
• Unexplained weight loss
• Night sweats
• Fever or frequent infections
• Enlarged spleen, causing a feeling of fullness or pain in the upper left abdomen
• Easy bruising or bleeding due to low platelets

If a patient on treatment shows rising BCR-ABL levels, it might mean the cancer is returning or resistant to current medicines.

Reference Ranges

Reference ranges for BCR-ABL depend on the testing method used, but typically results are interpreted as follows:

Sample Type and Collection Method

The BCR-ABL test can be done using either blood or bone marrow samples.

• Specimen Type:
  • Peripheral blood (used for initial testing and routine monitoring)
  • Bone marrow aspirate (used for confirmation at diagnosis)
• Collection Method:
  • Blood draw: A venous blood sample is taken from the arm.
  • Bone marrow aspiration: A small sample is taken from the hip bone under local anesthesia.
• Preparation:
  • No fasting or special preparation is needed before the test.
  • Patients should inform their doctor about ongoing medications or treatments.

Test Preparation

• You can eat and drink normally before the test.
• Avoid taking any unprescribed supplements or herbal medicines that could interfere with the result.
• If you’re undergoing treatment, make sure to schedule the test at regular intervals (as advised by your doctor) for accurate monitoring.
• Keep all your previous reports handy, as doctors often compare new results with older ones.

When to Consult a Doctor

You should consult a doctor or hematologist if you:

• Have been diagnosed with CML or Ph+ ALL and need test-based treatment monitoring.
• Experience new or worsening symptoms, such as fatigue, fever, or unexplained bleeding.
• Notice relapse symptoms after remission.
• Want to understand your treatment progress based on test results.

Immediate consultation is needed if your test shows rising BCR-ABL levels, as it might require a change in therapy.

Important Word Explanations

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