Web: | mayocliniclabs.com |
---|---|
Email: | mcl@mayo.edu |
Telephone: | 800-533-1710 |
International: | +1 855-379-3115 |
Values are valid only on day of printing. |
Diagnosis of acute promyelocytic leukemia (APL)
Detection of residual or recurrent APL
Monitoring the level of promyelocytic leukemia/retinoic acid receptor alpha (PML/RARA) in APL patients
See Acute Promyelocytic Leukemia: Guideline to Diagnosis and Follow-up in Special Instructions.
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 (PML/RARA) produced from the fusion gene can be detected using a 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 FISH.
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 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.
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.
The assay is reported in the form of a normalized ratio of promyelocytic leukemia/retinoic acid receptor alpha (PML-RARA) 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 PCR 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.
Promyelocytic leukemia/retinoic acid receptor alpha (PML/RARA) 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.
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 October;16(10):1959-1973
2. Adams J, Nassiri M: Acute Promyelocytic Leukemia A Review and Discussion of Variant Translocations. Arch Pathol Lab Med 2015;139:1308-1313
3. Kayser S, Schlenk RF, Platzbecker U: Management of patients with acute promyelocytic leukemia. Leukemia 2018;32:1277-1294
4. Ablain J, de The H: Revisiting the differentiation paradigm in acute promyelocytic leukemia. Blood 2011;117(22):5795-5802