This testing is used to detect the abnormal promyelocytic leukemia/retinoic acid receptor alpha or PML-RARAgene sequence. It is used to help diagnose acute promyelocytic leukemia (APL) in which the PML-RARA gene sequence is present, to guide treatment, to monitor response to treatment, and to monitor for disease recurrence.
A few different test methods are available to evaluate for PML-RARA, and they may be used for various purposes:
A molecular test (polymerase chain reaction, PCR) may be ordered to help establish the initial diagnosis of APL. A PML-RARA PCR test is typically ordered at the time of the initial diagnosis to establish a baseline value and then periodically to monitor a person's response to treatment and, if the person achieves remission, to monitor for recurrence. PCR will only detect the PML-RARA fusion, not the more rare combination of RARA with another gene.
A chromosome analysis may be used to help diagnose APL. This method can detect the more rare combination of RARA with a gene other than PML, so it may be used if one of the other test methods is negative but APL is still strongly suspected.
PML-RARA testing is often performed along with other blood and/or bone marrow tests if a doctor suspects that a person has leukemia and is trying to diagnose or rule out APL. Some of these other tests may include:
Testing is ordered when a doctor suspects that a person has APL. Initial testing may be indicated when a person has abnormal findings on a CBC and/or blood smear such as an increased or decreased number of white blood cells, decreased platelets, decreased red blood cells, and abnormal, immature white blood cells called promyelocytes, and nonspecific symptoms that may be related to leukemia such as:
Excessive bleeding, bruising, or inappropriate blood clotting
Early in APL, a person may have few or no symptoms. As time passes and normal blood cells are crowded out of the bone marrow and the number of abnormal leukemic cells increases, a person may experience anemia, prolonged bleeding, and recurrent infections. Those with APL may experience both bleeding and inappropriate clotting, with DIC (disseminated intravascular coagulation) as a potential life-threatening complication.
Once APL has been diagnosed, PML-RARA molecular testing is ordered periodically to monitor the response to treatment and monitor for recurrence.
A chromosome analysis may sometimes be ordered when a PML-RARA gene sequence is not detected and the doctor suspects another rearrangement involving the RARA gene may be present.
If a person has abnormal promyelocytes in the blood and bone marrow and has the PML-RARA gene sequence, then the person is diagnosed as having APL.
The presence of PML-RARA means the individual will likely benefit from treatment with all-trans retinoic acid (ATRA). This is a drug that can help promyelocytic leukemia cells to continue maturing. ATRA is typically effective in those cases where the PML-RARA fusion gene is present. A small percentage of people with APL have a fusion between RARA and a different gene, and they may or may not benefit from ATRA therapy depending upon the gene involved.
When monitoring treatment, a decrease in the amount of PML-RARA in the blood or bone marrow over time means the person is responding to treatment. If the number of cells that have PML-RARA drops below the test's detection limit and the person's blood cell counts are normal, then the person is considered to be in remission. An increase in PML-RARA levels over time indicates disease progression or recurrence.
If a person with APL is not positive for the PML-RARA gene sequence, then that person may not be given ATRA therapy and PML-RARA molecular testing cannot be used to monitor the person.
Both blood and bone marrow may be evaluated as part of the initial diagnosis, but follow-up monitoring is often performed on blood samples. There is significant test variability among laboratories using different test methods. Therefore, for a given person with APL, PML-RARA molecular testing should be done by the same laboratory. Rising and falling levels of PML-RARA are usually more important than a single test result.
This article was last reviewed on June 7, 2013. | This article was last modified on June 7, 2013.
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