The Test Sample
What is being tested?
Promyelocytic leukemia/retinoic acid receptor alpha or PML-RARA refers to an abnormal gene sequence that is associated with a specific type of leukemia. This test detects and measures PML-RARA in the blood or bone marrow to determine if an individual has acute promyelocytic leukemia (APL), a subtype of acute myeloid leukemia (AML). PML-RARA represents the rearrangement of genetic material on two chromosomes.
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 thousands of 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 PML-RARA gene sequence is one such acquired change (mutation) that is formed when pieces of chromosome 15 and chromosome 17 break off and switch places. The PML gene region in chromosome 15 then fuses with the RARA gene region in chromosome 17. This is referred to as reciprocal translocation, and this particular one is commonly expressed as t(15;17).
Normally, the PML gene codes for a protein that helps prevent uncontrolled cell growth and acts as a tumor suppressor. The RARA gene codes for a protein that is crucial for white blood cell (WBC) maturation, as these cells typically develop through several stages in the bone marrow before release into circulation. The mutated PML-RARA fusion gene codes for an abnormal fusion protein that does neither of these functions but instead leads to the uncontrolled production and accumulation of leukemic WBCs that do not mature or differentiate beyond the promyelocyte stage. As a large number of these abnormal cells start to crowd out the normal blood cell precursors in the bone marrow, signs and symptoms of leukemia start to emerge.
Up to 98% of cases of acute promyelocytic leukemia have a characteristic t(15;17) PML-RARA reciprocal chromosomal translocation. Occasionally, cases of APL have translocations involving the RARA gene and genes other than PML.
Testing detects the PML-RARA fusion gene or its transcripts, the RNA copies made by the cell from the abnormal gene sequence of DNA. The presence of the PML-RARA abnormality helps confirm the diagnosis of APL.
Testing can also help guide cancer therapy. Treatment of APL typically involves all-trans retinoic acid (ATRA), a drug that binds to retinoic acid receptors on cells. The drug can overcome the effect of the abnormal PML-RARA protein and allow the WBCs to continue maturing. This therapy works well in conjunction with chemotherapy but only in those cases where the PML-RARA fusion gene is present. The treatment results in remission in about 80-90% of these patients, according to the American Cancer Society. A small percentage of people with APL have a fusion between the RARA gene and a different gene, and they may or may not benefit from ATRA therapy dependending upon the specific gene involved.
There are several different types of PML-RARA tests available, including:
- Fluorescence in situ hybridization (FISH)
This test method uses fluorescent dye-labeled probes to "light up" the PML-RARA gene sequence when it is present. This method also determines the percentage of blood or bone marrow cells that contain the abnormal, fused PML-RARA gene. FISH can also be used to detect the variant translocations involving RARA and genes other than PML. This may help identify ATRA-resistant rearrangements.
- Genetic molecular testing
The polymerase chain reaction (PCR)-based tests detect and quantify PML-RARA gene transcripts, or gene product units, in a person's blood and/or bone marrow samples. The PML-RARA PCR test is quantitative, that is, it provides a general estimate of the number of PML-RARA gene sequences present.
- Chromosome analysis (cytogenetics or karyotyping)
This test method involves the evaluation of a person's chromosomes under a microscope to detect structural and/or numerical abnormalities. Cells in a sample of blood or bone marrow are examined to determine if the PML-RARA t(15;17) chromosome translocation is present. Other chromosomal abnormalities, such as translocations involving the RARA gene and genes other than PML can also be detected.
How is the sample collected for testing?
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.