At a Glance
Why Get Tested?
To help diagnose and monitor the treatment of chronic myelogenous leukemia (CML) and a type of acute lymphoblastic leukemia (ALL)
When to Get Tested?
Test Preparation Needed?
The Test Sample
What is being tested?
BCR-ABL refers to a gene sequence found in an abnormal chromosome 22 of some people with certain forms of leukemia. Humans normally have 23 pairs of chromosomes, including 22 pairs of non-sex-determining chromosomes (also known as autosomes) and 1 pair of sex chromosomes (XX for females, XY for males). Chromosomes contain a person's inherited genetic information. The genes that reside there form the blueprints for the production of countless proteins. Sometimes changes can occur to a person's chromosomes and/or genes during their lifetime, because of exposures to radiation, toxins, or for unknown reasons.
The BCR-ABL gene sequence is one such acquired change that is formed when pieces of chromosome 9 and chromosome 22 break off and switch places. When this occurs, the ABL region in chromosome 9 fuses with the BCR gene region in chromosome 22. This is referred to as reciprocal translocation and this particular one is commonly expressed as t(9;22). A derivative chromosome 22 that has the BCR-ABL gene sequence is known as the Philadelphia (Ph) chromosome. It is strongly associated with chronic myelogenous leukemia (CML) and, to a lesser extent, with acute lymphoblastic leukemia (ALL). At diagnosis, 90-95% of cases of CML show a characteristic t(9;22) BCR-ABL reciprocal chromosomal translocation.
These BCR-ABL gene sequences at the fusion site encode an abnormal protein. The abnormal BCR-ABL protein is a tyrosine kinase enzyme that is responsible for the development of CML and a type of ALL. It is the cause of uncontrolled growth of leukemic cells. When large numbers of abnormal leukemic cells start to crowd out the normal blood cell precursors in the bone marrow, signs and symptoms of leukemia start to emerge. Treatment of these leukemias typically involves a tyrosine kinase inhibitor (TKI).
Testing for BCR-ABL detects the Ph chromosome (the derivative chromosome 22) and BCR-ABL fusion gene or its transcripts, the RNA copies made by the cell from the abnormal stretches of DNA. The presence of the BCR-ABL abnormality confirms the clinical diagnosis in CML and a type of ALL.
There are several different types of BCR-ABL tests available, including:
- Cytogenetics (Chromosome analysis or Karyotyping)
This test looks at chromosomes under a microscope to detect structural and/or numerical abnormalities. Cells in a sample of blood or bone marrow are grown in the laboratory and then examined to determine if the Philadelphia chromosome is present. Other chromosomal abnormalities can also be detected.
- Fluorescence in situ hybridization (FISH)
This test method uses fluorescent dye-labeled probes to "light up" the BCR-ABL gene sequence when it is present and to determine the percentage of blood or bone marrow cells that contain the abnormal, fused BCR-ABL gene.
- Genetic molecular testing, qualitative or quantitative
The polymerase chain reaction (PCR)-based qualitative and quantitative tests detect and measure BCR-ABL gene transcripts, or gene product units, in a patient's blood and/or bone marrow samples. Variant mutations, for example BCR-ABL kinase domain mutations, can also be analyzed if indicated. These mutations are responsible for treatment resistance to tyrosine kinase inhibitors.
How is the sample collected for testing?
A blood sample is obtained by inserting a needle into a vein in the arm or a bone marrow sample is collected using a bone marrow aspiration and/or biopsy procedure.
NOTE: If undergoing medical tests makes you or someone you care for anxious, embarrassed, or even difficult to manage, you might consider reading one or more of the following articles: Coping with Test Pain, Discomfort, and Anxiety, Tips on Blood Testing, Tips to Help Children through Their Medical Tests, and Tips to Help the Elderly through Their Medical Tests.
Another article, Follow That Sample, provides a glimpse at the collection and processing of a blood sample and throat culture.
Is any test preparation needed to ensure the quality of the sample?
No test preparation is needed.
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NOTE: This article is based on research that utilizes the sources cited here as well as the collective experience of the Lab Tests Online Editorial Review Board. This article is periodically reviewed by the Editorial Board and may be updated as a result of the review. Any new sources cited will be added to the list and distinguished from the original sources used.
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