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PML-RARA

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Also known as: Promyelocytic Leukemia/Retinoic Acid Receptor Alpha [PML-RARA t(15;17)(q22;q12)]; Acute Promyelocytic Leukemia; AML-M3
Formal name: [PML-RARA t(15;17)]

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The Test Sample

What is being tested?

Promyelocytic leukemia/retinoic acid receptor alpha or PML-RARA refers to an abnormal fusion gene sequence. It is a specific rearrangement of genetic material from two separate chromosomes (chromosomal translocation) and 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).

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). The genetic makeup of a person is contained on her/his chromosomes. The genes that reside on chromosomes 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. These exposures could lead to gene mutations or to chromosome translocations.

The PML-RARA fusion gene sequence is one such acquired change (mutation) that is formed when pieces of chromosome 15 and chromosome 17 break off and switch places (translocate). 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. In about 2% of APL cases, other translocations involving the RARA gene and genes other than PML have been reported.

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 direct APL therapy and monitor minimal residual disease, which could be fatal. Treatment of APL typically involves all-trans retinoic acid (ATRA), a drug that binds to retinoic acid receptors in cells. The drug can overcome the effect of the abnormal PML-RARA protein and induce downstream signaling and maturation of WBCs. 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 based upon the specific gene involved.

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 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.