What is being tested?
BCR-ABL1 refers to a sequence found in an abnormal 22 of some people with certain forms of leukaemia.
Humans have 23 pairs of chromosomes containing inherited genetic information in each cell. These chromosomes are made of , and contain the blueprints in the form of for producing the that our bodies rely on to function properly. When there are changes in the chromosomes or genes, abnormal proteins may be produced which have abnormal function. Some genetic changes are inherited from a parent (germline changes). Other genetic changes occur during a person’s lifetime (somatic or acquired changes). These acquired changes can happen due to exposure to various environmental factors (e.g., radiation, certain chemicals) but more often for unknown reasons.
The BCR-ABL1 fusion gene sequence is one such acquired change that is formed when pieces of chromosome 9 and chromosome 22 break off and switch places. This type of change is called a reciprocal and is often abbreviated as t(9;22). When this occurs, the ABL1 region in chromosome 9 fuses with the BCR region in chromosome 22. The resulting derivative chromosome 22 which has the BCR-ABL1 fusion gene sequence is known as the Philadelphia (Ph) chromosome.
The BCR-ABL1 fusion gene encodes an abnormal protein. This abnormal protein is a type of signalling protein called , which has become abnormally and permanently switched “on”. This leads to uncontrolled cell growth and is responsible for the development of CML and a type of ALL. When large numbers of abnormal leukaemic cells start to crowd out the normal blood cell in the , signs and symptoms of leukaemia start to emerge. Treatment of these leukaemias typically involves a such as Imatinib (Glivec®), given as daily oral tablets.
Testing for BCR-ABL1 detects the Philadelphia chromosome, the BCR-ABL1 fusion gene, or BCR-ABL1 transcripts, which are the copies made by the cell from the abnormal fusion gene. The presence of the BCR-ABL1 abnormality confirms the clinical diagnosis of CML or a type of ALL.
There are several different types of BCR-ABL1 tests available, including:
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.
This test method uses differently-coloured fluorescent dye-labelled probes to "light up" the BCR and the ABL1 gene sequences. Cells are examined under a microscope to determine the proportion if any where the coloured dots are fused together, indicating a BCR-ABL1 translocation. This is a more sensitive method of detection than cytogenetics.
-based qualitative and quantitative tests detect and measure the level of BCR-ABL1 gene transcripts, or gene product units, in a patient's blood and/or bone marrow samples. This is the most sensitive test for BCR-ABL1. It is used to monitor the response to treatment with tyrosine kinase inhibitors (TKIs). It is also used to diagnose the minority of cases negative for the Philadelphia chromosome.
Secondary mutations may arise within BCR-ABL1 in the kinase domain. These can be detected by DNA sequencing methods. These mutations may be responsible for treatment resistance to TKIs. If the response to treatment is suboptimal, mutational analysis may tell your doctor which TKIs will be more effective.
How is the sample collected for testing?
A blood sample is taken 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
Is any test preparation needed to ensure the quality of the sample?
No test preparation is needed.