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HelpTest Code PMLR PML::RARA Quantitative, PCR, Varies
Reporting Name
PML/RARA Quantitative, PCRUseful For
Diagnosis of acute promyelocytic leukemia (APL)
Detection of residual or recurrent APL
Monitoring the level of PML::RARA (promyelocytic leukemia/retinoic acid receptor alpha) in APL patients
Testing Algorithm
For more information see Acute Promyelocytic Leukemia: Guideline to Diagnosis and Follow-up
Performing Laboratory
Mayo Clinic Laboratories in Rochester
Specimen Type
VariesOrdering Guidance
This assay may not detect rare, unusual PML::RARA fusions. Therefore, if the assay is going to be used for monitoring after treatment, the test should be performed at the time of diagnosis to ensure that the test gives a positive result.
Shipping Instructions
1. Refrigerated specimens must arrive within 5 days of collection, and ambient specimens must arrive within 3 days of collection.
2. Collect and package specimen as close to shipping time as possible.
Necessary Information
The following information is required:
1. Pertinent clinical history
2. Date of collection
3. Specimen source (blood or bone marrow)
Specimen Required
Submit only 1 of the following specimens:
Specimen Type: Whole blood
Container/Tube:
Preferred: Lavender top (EDTA)
Acceptable: Yellow top (ACD)
Specimen Volume: 10 mL
Collection Instructions:
1. Invert several times to mix blood.
2. Send whole blood specimen in original tube. Do not aliquot.
3. Label specimen as blood.
Specimen Type: Bone marrow
Container/Tube:
Preferred: Lavender top (EDTA)
Acceptable: Yellow top (ACD)
Specimen Volume: 4 mL
Collection Instructions:
1. Invert several times to mix bone marrow.
2. Send bone marrow specimen in original tube. Do not aliquot
3. Label specimen as bone marrow.
Specimen Minimum Volume
Blood: 8 mL; Bone Marrow: 2 mL
Specimen Stability Information
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| Varies | Refrigerated (preferred) | 5 days | PURPLE OR PINK TOP/EDTA |
| Ambient | 72 hours | PURPLE OR PINK TOP/EDTA |
Special Instructions
Reference Values
An interpretive report will be provided.
If positive, a value representing a ratio of PML::RARA fusion transcript to the control gene ABL1 expressed as a percentage will be reported.
Day(s) Performed
Monday through Saturday
Test Classification
This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.CPT Code Information
81315-PML/RAR-alpha (t(15;17)), (PML-RARA regulated adaptor molecule 1) (eg, promyelocytic leukemia) translocation analysis; all breakpoints (eg, intron 3, intron 6 and variable in exon 6), qualitative or quantitative
LOINC Code Information
| Test ID | Test Order Name | Order LOINC Value |
|---|---|---|
| PMLR | PML/RARA Quantitative, PCR | In Process |
| Result ID | Test Result Name | Result LOINC Value |
|---|---|---|
| 39469 | PMLR Result | No LOINC Needed |
| MP012 | Specimen Type | 31208-2 |
| 19449 | Interpretation | 69047-9 |
Clinical Information
Acute promyelocytic leukemia (APL) accounts for 5% to 10% of acute myeloid leukemia and, generally, has a good prognosis with current treatment protocols. APL cells contain a fusion gene comprised of the downstream sequences of the retinoic acid receptor alpha gene (RARA) fused to the promoter region and upstream sequences of one of several genes, the most common (>80%) being the promyelocytic leukemia gene (PML). The fusion gene is designated PML::RARA and may be seen in a karyotype as t(15;17)(q22;q12). Messenger RNA produced from the fusion gene can be detected using a polymerase chain reaction (PCR)-based assay and indicates the presence of neoplastic cells. The PCR-based assay has greater sensitivity than standard methods such as morphology review, karyotyping, or fluorescence in situ hybridization.
Recent studies have indicated that sensitive monitoring is important because the majority of patients who remain PCR positive, or become PCR positive again following treatment, will relapse and will likely benefit from early intervention for residual/recurrent disease. This quantitative assay allows PML::RARA levels to be monitored rather than simply detecting the presence or absence of disease.
Interpretation
The assay is reported in the form of a normalized ratio of PML::RARA (promyelocytic leukemia/retinoic acid receptor alpha) fusion transcript to the control gene ABL1 expressed as a percentage, which is an estimate of the level of PML::RARA RNA present in the specimen, expressed in relation to the level of RNA from an internal control gene (ABL1). The normalized ratio has no units but is directly related to the level of PML::RARA detected (ie, larger numbers indicate higher levels of PML::RARA and smaller numbers indicate lower levels). A relative expression value minimizes variability in the RNA levels measured in separate specimens tested at different times. Although a quantitative polymerase chain reaction assay is performed, the precision of the assay is such that results must be considered semiquantitative, and it is recommended that only log changes be considered significant. Critical results, such as a change in the status of positivity, should be repeated on a separate specimen to verify the result.
Cautions
PML::RARA (promyelocytic leukemia/retinoic acid receptor alpha) levels can only be compared reliably if tested in the same laboratory using the same procedure each time.
This assay will only detect PML::RARA RNA and will not detect RNA from the less common RARA fusion genes.
Clinical Reference
1. Grimwade D, Lo Coco F. Acute promyelocytic leukemia: a model for the role of molecular diagnosis and residual disease monitoring in directing treatment approach in acute myeloid leukemia. Leukemia. 2002;16(10):1959-1973
2. Adams J, Nassiri M. Acute promyelocytic leukemia: A review and discussion of variant translocations. Arch Pathol Lab Med. 2015;139(10):1308-1313
3. Kayser S, Schlenk RF, Platzbecker U. Management of patients with acute promyelocytic leukemia. Leukemia. 2018;32(6):1277-1294
4. Ablain J, de The H. Revisiting the differentiation paradigm in acute promyelocytic leukemia. Blood. 2011;117(22):5795-5802
Method Description
Total RNA is extracted from blood or bone marrow and reverse transcribed to generate complementary DNA. Quantitative real-time polymerase chain reaction is performed using the LightCycler instrument platform (Roche) and the data analyzed using the dedicated software for relative quantification with calibrator normalization. Results are provided as a normalized relative value of PML::RARA/ABL1 messenger RNA (mRNA) with a reproducible analytical sensitivity of 0.003%(Unpublished Mayo method).
The normalized ratio is a relative quantification calculation as follows:
|
Normalized ratio*= |
PML::RARA (sample) ABL1 (sample) |
|
PML::RARA (calibrator) ABL1 (calibrator) |
*Where ABL1 mRNA is used to normalize variations in RNA quality and calibrator mRNA from a PML::RARA-positive cell line is used to normalize variations in run conditions.
Report Available
4 to 8 daysSpecimen Retention Time
Blood/Bone marrow: 2 weeks; Extracted RNA: 3 monthsReject Due To
| Gross hemolysis | Reject |
| Moderately to severely clotted | Reject |
Method Name
Quantitative, Real-Time Polymerase Chain Reaction (PCR)
Secondary ID
84114Forms
1. Hematopathology Patient Information (T676)
2. If not ordering electronically, complete, print, and send a Hematopathology/Cytogenetics Test Request (T726) with the specimen.