For URGENT DIAGNOSTIC APL Testing:
Monday thru Friday (8 a.m.-5 p.m.): Notify Hematopathology at 215-980-9781 immediately to arrange testing.
Evenings, Weekends and Holidays: Call the Hematopathology Fellow on call (215-265-1089) to arrange testing.
Inpatient Approval Requirements
No
Patient Preparation
None
Collection Container
Collect
Blood: minimum 7 ml of blood in an EDTA pink top tube
Bone Marrow: minimum 0.5-1 ml Bone Marrow in EDTA lavender top tube
Cells from Flow Cytometry in sterile container, volume dependent upon cellularity
Pediatric Collection
Contact the Molecular Laboratory at 215-662-6121 to arrange testing.
Specimen Preparation
Do not spin or separate.
Storage/Transport Temperature
Refrigerated (preferred) or Room Temperature
Stability (from collection to initiation)
Stable refrigerated for 72 hours (preferred storage temperature), and at room temperature for <4 hours.
Unacceptable Conditions
Clotted, hemolyzed, heparinized, or frozen specimens
Specimens older than 72 hours
Notes
This test was developed and its performance characteristics determined by the Molecular Pathology Laboratory in the Department of Pathology and Laboratory Medicine in the University of Pennsylvania Health System at the Hospital of the University of Pennsylvania 3400 Spruce Street, Philadelphia, PA 19104. It has not been cleared or approved by the US Food and Drug Administration (FDA). The FDA does not require this test to go through premarket FDA review. This test is used for clinical purposes. It should not be regarded as investigational or for research. This laboratory is certified under the Clinical Laboratory Improvement Amendments (CLIA) as qualified to perform high complexity clinical laboratory testing.
Processing - HUP
Do not spin or separate. Place sample and copy of requisition in Molecular Pathology sample box in Central Receiving.
Reference Interval
Not Detected
Interpretive Data and Information
Rare variant RARA rearrangements including, but not limited to: t(11;17)(q23;q21) ZBTB16/RARA, t(5;17)(q35;q21) NPM1/RARA, t(17;17)(q21;q21) STAT5B/RARA and t(11;17)(q13;q21) NUMA1/RARA are NOT detected by this assay. This assay detects but cannot distinguish between intron 6 (long, bcr1) and exon 6 (variable, bcr-2) breakpoints in PML/RARA fusions. Additionally, due to technical limitations of the PML/RARA assay, this method may not be able to accurately classify or reliably detect a small subset of PML/RARA fusions with exon 6 breakpoints. Given these limitations, when testing for residual disease, a result of "not detected" should be interpreted with caution if the initial diagnostic specimen was not evaluated by this assay to assure that a fusion transcript is detectable. If the PML/RARA fusion transcript is not detected by this assay and clinical suspicion remains high for APL in a diagnostic setting, evaluation for rare variant genomic rearrangements by alternative methods, such as FISH or conventional cytogenetics, should be considered. The limit of detection of this assay is approximately 10 copies of fusion transcript per reaction which equates to approximately 0.01% neoplastic cell.
Clinical Significance
The PML/RARA fusion transcript, typically arising from the t(15;17)(q24;q21), is consistent with acute promyelocytic leukemia (APL). The t(15;17) is found in approximately 5-8% of acute myeloid leukemia (AML) cases. In diagnostic settings, the absence of PML/RARA fusion transcripts by this assay significantly reduces, but does not entirely exclude, the presence of this gene fusion. In the evaluation of minimal residual disease, an undetectable level of the PML/RARA fusion transcript following therapy for APL is associated with a lower risk of clinical relapse.
CPT Codes
81315, 81316, G0452
LOINC
21551-7
Collection & Processing
Ordering Recommendations
For URGENT DIAGNOSTIC APL Testing:
Monday thru Friday (8 a.m.-5 p.m.): Notify Hematopathology at 215-980-9781 immediately to arrange testing.
Evenings, Weekends and Holidays: Call the Hematopathology Fellow on call (215-265-1089) to arrange testing.
Inpatient Approval Requirements
No
Patient Preparation
None
Collection Container
Collect
Blood: minimum 7 ml of blood in an EDTA pink top tube
Bone Marrow: minimum 0.5-1 ml Bone Marrow in EDTA lavender top tube
Cells from Flow Cytometry in sterile container, volume dependent upon cellularity
Pediatric Collection
Contact the Molecular Laboratory at 215-662-6121 to arrange testing.
Specimen Preparation
Do not spin or separate.
Storage/Transport Temperature
Refrigerated (preferred) or Room Temperature
Stability (from collection to initiation)
Stable refrigerated for 72 hours (preferred storage temperature), and at room temperature for <4 hours.
Unacceptable Conditions
Clotted, hemolyzed, heparinized, or frozen specimens
Specimens older than 72 hours
Notes
This test was developed and its performance characteristics determined by the Molecular Pathology Laboratory in the Department of Pathology and Laboratory Medicine in the University of Pennsylvania Health System at the Hospital of the University of Pennsylvania 3400 Spruce Street, Philadelphia, PA 19104. It has not been cleared or approved by the US Food and Drug Administration (FDA). The FDA does not require this test to go through premarket FDA review. This test is used for clinical purposes. It should not be regarded as investigational or for research. This laboratory is certified under the Clinical Laboratory Improvement Amendments (CLIA) as qualified to perform high complexity clinical laboratory testing.
CR&P Information
Processing - HUP
Do not spin or separate. Place sample and copy of requisition in Molecular Pathology sample box in Central Receiving.
Result Interpretation
Reference Interval
Not Detected
Interpretive Data and Information
Rare variant RARA rearrangements including, but not limited to: t(11;17)(q23;q21) ZBTB16/RARA, t(5;17)(q35;q21) NPM1/RARA, t(17;17)(q21;q21) STAT5B/RARA and t(11;17)(q13;q21) NUMA1/RARA are NOT detected by this assay. This assay detects but cannot distinguish between intron 6 (long, bcr1) and exon 6 (variable, bcr-2) breakpoints in PML/RARA fusions. Additionally, due to technical limitations of the PML/RARA assay, this method may not be able to accurately classify or reliably detect a small subset of PML/RARA fusions with exon 6 breakpoints. Given these limitations, when testing for residual disease, a result of "not detected" should be interpreted with caution if the initial diagnostic specimen was not evaluated by this assay to assure that a fusion transcript is detectable. If the PML/RARA fusion transcript is not detected by this assay and clinical suspicion remains high for APL in a diagnostic setting, evaluation for rare variant genomic rearrangements by alternative methods, such as FISH or conventional cytogenetics, should be considered. The limit of detection of this assay is approximately 10 copies of fusion transcript per reaction which equates to approximately 0.01% neoplastic cell.
Clinical Significance
The PML/RARA fusion transcript, typically arising from the t(15;17)(q24;q21), is consistent with acute promyelocytic leukemia (APL). The t(15;17) is found in approximately 5-8% of acute myeloid leukemia (AML) cases. In diagnostic settings, the absence of PML/RARA fusion transcripts by this assay significantly reduces, but does not entirely exclude, the presence of this gene fusion. In the evaluation of minimal residual disease, an undetectable level of the PML/RARA fusion transcript following therapy for APL is associated with a lower risk of clinical relapse.
Testing Updates
Billing Codes
CPT Codes
81315, 81316, G0452
LOINC
21551-7
Ordering Information
Cerner Orderable
Case - Acute Promyelocytic Leukemia
C2008115
Penn Chart Orderable
PML/RARA, Qualitative
Performing Lab
Molecular Pathology
Performed
At least weekly ( more frequently as testing volume dictates), 8 a.m. - 8 p.m.
Reported
7 days
Methodology
RNA isolation and reverse transcription Polymerase Chain Reaction (RT-PCR) followed by multiplex real-time PCR.
