Test Id : APLDF
Acute Promyelocytic Leukemia-PML::RARA fusion, Expedited Diagnostic FISH, Varies
Useful For
Suggests clinical disorders or settings where the test may be helpful
Detecting, at diagnosis, acute promyelocytic leukemia (APL)
This test should not be used to screen for residual APL.
Highlights
This test is automatically expedited within the FISH laboratory. Test results are finalized and released 7 days a week.
All attempts will be made to provide final results the day of specimen receipt at Mayo Clinic Laboratories. Some results may not be reported until the following day due to established cutoff times or if additional RARA testing is required.
Reflex Tests
Lists tests that may or may not be performed, at an additional charge, depending on the result and interpretation of the initial tests.
| Test Id | Reporting Name | Available Separately | Always Performed |
|---|---|---|---|
| APLDB | Probe, Each Additional (APLDF) | No, (Bill Only) | No |
Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.
This test includes a charge for the probe application, analysis, and professional interpretation of results for 1 probe set (2 individual fluorescence in situ hybridization [FISH] probes). Additional charges will be incurred for all reflex or additional probe sets performed. Analysis charges will be incurred based on the number of cells analyzed per probe set. If no cells are available for analysis, no analysis charges will be incurred.
This test should only be ordered at the time of diagnosis.
In the absence of PML::RARA fusion, when an extra RARA FISH signal is identified, reflex testing using the break-apart RARA probe set will be performed to resolve or confirm RARA rearrangement concerns. If additional RARA testing is required, results will be delayed until the next business day.
Appropriate ancillary probes may be performed at consultant discretion to render comprehensive assessment. Any additional probes will have the results included within the final report and will be performed at an additional charge.
Method Name
A short description of the method used to perform the test
Fluorescence In Situ Hybridization (FISH)
NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.
Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test
Aliases
Lists additional common names for a test, as an aid in searching
Acute myeloid leukemia (AML)
Acute promyelocytic leukemia (APL)
AML (acute myeloid leukemia)
AMPL
PML/RARA
t(15;17)(q24.1;q21.2)
Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.
This test includes a charge for the probe application, analysis, and professional interpretation of results for 1 probe set (2 individual fluorescence in situ hybridization [FISH] probes). Additional charges will be incurred for all reflex or additional probe sets performed. Analysis charges will be incurred based on the number of cells analyzed per probe set. If no cells are available for analysis, no analysis charges will be incurred.
This test should only be ordered at the time of diagnosis.
In the absence of PML::RARA fusion, when an extra RARA FISH signal is identified, reflex testing using the break-apart RARA probe set will be performed to resolve or confirm RARA rearrangement concerns. If additional RARA testing is required, results will be delayed until the next business day.
Appropriate ancillary probes may be performed at consultant discretion to render comprehensive assessment. Any additional probes will have the results included within the final report and will be performed at an additional charge.
Specimen Type
Describes the specimen type validated for testing
Varies
Ordering Guidance
This test is intended for diagnostic samples only when PML::RARA fusion is presumed and targeted PML and RARA fluorescence in situ hybridization (FISH) probes are needed to diagnose acute promyelocytic leukemia (APL).
Complete acute myeloid leukemia (AML) diagnostic FISH panel tests for adults and pediatric patients are also available. AML panel tests will be automatically prioritized by the laboratory when PML::RARA fusion is present. Most often, AML panel tests found with PML::RARA fusion will be reported the next business day from receipt in the Genomics laboratory. Same day testing is not available for panel testing. If panel testing is warranted, order either AMLFA / Adult Acute Myeloid Leukemia Panel, FISH, Varies or AMLFP / Pediatric Acute Myeloid Leukemia Panel, FISH, Varies, as appropriate based on patient age.
This test should not be used to screen for residual AML or when the diagnosis of APL is not strongly suggested. Monitoring patients known to have PML::RARA fusion should be performed by quantitative reverse transcription-polymerase chain reaction (RT-PCR) testing and not FISH testing. If the specimen does not meet the criteria for RT-PCR, follow-up FISH testing for PML::RARA fusion should be ordered as AMLMF / Acute Myeloid Leukemia (AML), Specified FISH, Varies with a PML/RARA specific probe request.
If this test is received in the laboratory concurrently with an order for either AMLFA / Adult Acute Myeloid Leukemia Panel, FISH, Varies or AMLFP / Pediatric Acute Myeloid Leukemia Panel, FISH, Varies, panel testing will be held pending the results of this test. Ordering an AML panel test concurrently with this test will result in an approximate 1 business day delay of the panel test reporting. If PML::RARA fusion is detected, the AMLFA or AMLFP panel test will be cancelled by the laboratory. If no fusion is identified, the complete AML FISH panel test will be performed, except for the PML/RARA FISH probe set.
If the entire AML FISH panel is preferred for an adult patient (aged 31 years or older), order AMLFA / Adult Acute Myeloid Leukemia panel, FISH, Varies.
If the entire AML FISH panel is preferred for a pediatric patient (aged 30 years or younger), order AMLFP / Pediatric Acute Myeloid Leukemia panel, FISH, Varies.
If upfront break-apart RARA FISH testing is desired, order AMLMF / Acute Myeloid Leukemia (AML), Specified FISH, Varies. Results will be reported the next business day.
For more information see Acute Promyelocytic Leukemia: Guideline to Diagnosis and Follow-up
Additional Testing Requirements
At diagnosis, PMLR / PML::RARA Quantitative, PCR, Varies should be performed in parallel with this test.
At follow-up, only PMLR / PML::RARA Quantitative, PCR, Varies should be performed.
Shipping Instructions
Advise Express Mail or equivalent if not on courier service.
Necessary Information
1. A reason for testing must be provided. If this information is not provided, an appropriate indication for testing may be entered by Mayo Clinic Laboratories.
2. A flow cytometry and/or a bone marrow pathology report should be submitted with each specimen. The laboratory will not reject testing if this information is not provided, but appropriate testing and interpretation may be compromised or delayed.
3. If a result callback by phone is needed after finalized results are released, the ordering healthcare professional must supply the name and direct phone number of a licensed physician (MD or DO) at the time the order is received.
-Result callbacks are only available during regular business hours.
-Preliminary results or exact times the finalized report will be available will not be provided under any circumstances.
ORDER QUESTIONS AND ANSWERS
| Question ID | Description | Answers |
|---|---|---|
| GC168 | Reason for Referral | |
| GC169 | Specimen |
Whole blood ACD Bone marrow ACD Whole blood Na Hep Bone marrow Na Hep Whole blood EDTA Bone marrow EDTA |
Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing
Submit only 1 of the following specimens:
Preferred
Specimen Type: Bone marrow
Container/Tube:
Preferred: Yellow top (ACD)
Acceptable: Green top (sodium heparin) or lavender top (EDTA)
Specimen Volume: 2 to 3 mL
Collection Instructions:
1. It is preferable to send the first aspirate from the bone marrow collection.
2. Invert several times to mix bone marrow.
3. Send bone marrow in original tube. Do not aliquot.
Acceptable
Specimen Type: Whole blood
Container/Tube:
Preferred: Yellow top (ACD)
Acceptable: Green top (sodium heparin) or lavender top (EDTA)
Specimen Volume: 6 mL
Collection Instructions:
1. Invert several times to mix blood.
2. Send whole blood in original tube. Do not aliquot.
Special Instructions
Library of PDFs including pertinent information and forms related to the test
Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the testing laboratory. The minimum volume is sufficient for one attempt at testing.
Bone marrow: 1 mL; Whole blood: 2 mL
Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected
Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| Varies | Ambient (preferred) | ||
| Refrigerated | |||
Useful For
Suggests clinical disorders or settings where the test may be helpful
Detecting, at diagnosis, acute promyelocytic leukemia (APL)
This test should not be used to screen for residual APL.
Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.
This test includes a charge for the probe application, analysis, and professional interpretation of results for 1 probe set (2 individual fluorescence in situ hybridization [FISH] probes). Additional charges will be incurred for all reflex or additional probe sets performed. Analysis charges will be incurred based on the number of cells analyzed per probe set. If no cells are available for analysis, no analysis charges will be incurred.
This test should only be ordered at the time of diagnosis.
In the absence of PML::RARA fusion, when an extra RARA FISH signal is identified, reflex testing using the break-apart RARA probe set will be performed to resolve or confirm RARA rearrangement concerns. If additional RARA testing is required, results will be delayed until the next business day.
Appropriate ancillary probes may be performed at consultant discretion to render comprehensive assessment. Any additional probes will have the results included within the final report and will be performed at an additional charge.
Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Acute myeloid leukemia (AML) is one of the most common adult leukemias, with almost 10,000 new cases diagnosed per year. AML also comprises 15% of pediatric acute leukemia and accounts for the majority of infant (<1 year old) leukemia. Acute promyelocytic leukemia (APL) is a subtype of AML and is most often associated with t(15;17)(q24;q21) with subsequent fusion of the PML gene with the RARA gene.
Real-time quantitative polymerase chain reaction is currently the standard method for molecular monitoring in APL(1),. fluorescence in situ hybridization is not recommended for APL monitoring.
Reference Values
Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
An interpretive report will be provided
Interpretation
Provides information to assist in interpretation of the test results
Detection of PML::RARA (promyelocytic leukemia/retinoic acid receptor alpha) fusion confirms the clinical diagnosis of acute promyelocytic leukemia (APL). In rare cases, APL is caused by fusion between RARA and one of several other partner genes. When APL is highly suspected and fluorescence in situ hybridization (FISH) shows no PML::RARA fusion, FISH for RARA rearrangement is recommended. A PML-RARA fusion positive APL may also have other clonal chromosome abnormalities that can be detected by chromosome analysis. A PML::RARA fusion may be accompanied by gene mutations that can be detected by polymerase chain reaction (PCR) or sequencing. Disease monitoring for APL is preferably done by quantitative PCR for the PML::RARA fusion gene transcripts.
Cautions
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
This test is not approved by the US Food and Drug Administration and it is best used as an adjunct to clinical and pathologic information.
If additional RARA testing is required, results will be delayed until the next business day. The laboratory is unable to provide preliminary results.
This test will only utilize the fluorescence in situ hybridization (FISH ) algorithm described in the testing algorithm. The break-apart RARA FISH probe set cannot be preemptively added to this test.
This assay may not detect rare, unusual PML::RARA fusion.
Bone marrow is the preferred specimen type for this FISH test. If bone marrow is not available, a blood specimen may be used if there are circulating myeloblasts in the blood specimen (as verified by a hematopathologist).
If no FISH signals are observed post-hybridization, the case will be released indicating a lack of FISH results.
Clinical Reference
Recommendations for in-depth reading of a clinical nature
1. Pollyea DA, Altman JK, Assi R, et al. Acute Myeloid Leukemia, Version 3.2023, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2023;21(5):503-513. doi:10.6004/jnccn.2023.0025
2. WHO Classification of Tumours Editorial Board, eds. Haematolymphoid tumours. 5th ed. IARC Press; 2024. WHO Classification of Tumours, Volume 11
3. De Braekeleer E, Douet-Guilbert N, De Braekeleer M. RARA fusion genes in acute promyelocytic leukemia: a review. Expert Rev Hematol. 2014;7(3):347-357
4. Sanz MA, Fenaux P, Tallman MS, et al. Management of acute promyelocytic leukemia: updated recommendations from an expert panel of the European LeukemiaNet. Blood. 2019;133(15):1630-1643
5. Mannan A, Muhsen I, Barragan E, et al. Genotypic and phenotypic characteristics of acute promyelocytic leukemia translocation variants. Hematol Oncol Stem Cell Ther. 2020:13(4):189-201
6. Gagnon MF, Berg HE, Meyer RG, et al. Typical, atypical and cryptic t(15;17)(q24;q21) (PML::RARA) observed in acute promyelocytic leukemia: A retrospective review of 831 patients with concurrent chromosome and PML::RARA dual-color dual-fusion FISH studies. Genes Chromosomes Cancer. 2022;61(10):629-634. doi:10.1002/gcc.23070
7. Dohner H, Wei AH, Appelbaum FR, et al. Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN. Blood. 2022;140(12):1345-1377. doi:10.1182/blood.2022016867
Method Description
Describes how the test is performed and provides a method-specific reference
This test is performed using a commercially available probe set. A dual-color, dual-fusion fluorescence in situ hybridization (D-FISH) strategy probe set is used to detect PML::RARA fusion. Following probe hybridization, 200 interphase nuclei are scored, and the results are expressed as the percent abnormal nuclei. When needed to resolve a potential RARA disruption, 100 interphase nuclei are scored using the dual-color break-apart RARA FISH probe.(Unpublished Mayo method)
PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information
Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.
Monday through Sunday
Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.
Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded
Performing Laboratory Location
Indicates the location of the laboratory that performs the test
Fees :
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.
- Authorized users can sign in to Test Prices for detailed fee information.
- Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
- Prospective clients should contact their account representative. For assistance, contact Customer Service.
Test Classification
Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.
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
Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.
CPT codes are provided by the performing laboratory.
CPT codes are provided by the performing laboratory.
88271x2, 88275x1, 88291x1- FISH Probe, Analysis, Interpretation; 1 probe set
88271x2, 88275x1-FISH Probe, Analysis; each additional probe set (if appropriate)
LOINC® Information
Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and results codes of this test. LOINC values are provided by the performing laboratory.
| Test Id | Test Order Name | Order LOINC Value |
|---|---|---|
| APLDF | APL - PML::RARA fusion, FISH, BL/BM | 77031-3 |
| Result Id | Test Result Name |
Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
|
|---|---|---|
| 622914 | Result Summary | 50397-9 |
| 622915 | Interpretation | 77031-3 |
| 622916 | Result Table | 93356-4 |
| 622917 | Result | 62356-1 |
| GC168 | Reason for Referral | 42349-1 |
| GC169 | Specimen | 31208-2 |
| 622918 | Source | 31208-2 |
| 622919 | Method | 85069-3 |
| 622920 | Additional Information | 48767-8 |
| 622921 | Disclaimer | 62364-5 |
| 622922 | Released By | 18771-6 |