PML/RAR? T(15;17) TRANSLOCATION BY RT-PCR

Code
000.0000
Name
PML/RAR? T(15;17) TRANSLOCATION BY RT-PCR
Category
None
Department
Send-Out
Start Date
Expiration Date
Synonyms
Acute myeloid leukemia (AML)
CPT Codes
83891; 83896x3; 83898x3; 83902; 83912
Site
SBMF
Reference Test
44929
ATLAS Test Code

Specimen Information

Type

Lavender, EDTA Whole Blood

Volume

1.0 mL

Transport Info

Samples must be received at ARUP within 48 hours of collection due to lability of RNA
Refrigerated

Fasting Required?
False
Patient Instructions

Reference Range

See report

Methodology

Reverse Transcription Polymerase Chain Reaction (RT-PCR)

Clinical Significance

A positive result indicates the presence of a PML/RARa fusion transcript. A negative result indicates the absence of a PML/RARa fusion transcript within the sample. The t(15;17) chromosomal translocation which leads to the PML/RARa fusion transcript is strongly associated with acute promyelocytic leukemia (APL). The detection of this highly characteristic abnormality is useful in the accurate diagnosis of APL. These tumor-specific markers can also be used to monitor the remission status of affected patients. RT-PCR provides a rapid alternative to cytogenetic analysis and may identify PML/RARa gene rearrangement in the absence of detectable t(15;17) by the latter technique. This test is not intended for minimal residual disease detection. Results of this test must always be interpreted in the context of morphologic and other relevant data, and should not be used alone for a diagnosis of malignancy.

Acute promyelocytic leukemia (APL) is a distinctive form of acute myelogenous leukemia (AML). It accounts for approximately ten percent of AML and is characterized by a proliferation of malignant promyelocytes in the bone marrow, often with a discrepant leukopenic peripheral blood smear. APL is classified as AML or as M3 in the FAB scheme for acute leukemias. Patients with APL have distinctive clinical features. These individuals are generally younger than the typical AML patient, have a better prognosis, and almost always have disseminated intravascular coagulation (DIC). This coagulopathy becomes more severe with chemotherapy and may lead to patient demise during treatment. Therefore, proper subclassification of acute leukemia as APL is critical for optimal patient management (i.e., to alert the clinician that there is a significant risk of DIC). In addition, alternative strategies are used by hematologists/oncologists to treat APL. Specifically, all-trans retinoic acid (ATRA), a relatively non-toxic agent, permits myeloid differentiation of the leukemic promyelocytes and is used as a first-line agent in the treatment of this entity; this is followed by standard chemotherapy. In summary, immediate patient survival and important clinical decisions are based on accurate diagnosis of APL. Cytogenetic and molecular tests can be used to establish a definitive diagnosis of APL. There is a strong association of t(15;17), and its molecular equivalent PML/RARa gene rearrangement, with this subtype of AML. In fact, the utility of ATRA therapy is based on changes induced in the retinoic acid receptor a (RARa) gene by this translocation. Moreover, the response to ATRA in patients with AAPL is directly related to the presence of PML/RARa gene rearrangement (i.e., some AML -- M3 classified in the FAB scheme -- do not have this molecular characteristic and have no response to ATRA). Therefore, the molecular definition of APL appears to have more clinical relevance than the morphologic one. Cytogenetic analysis is capable of detecting t(15;17) in many cases of APL; however, up to 30 percent of cases may be negative with this technique. In contrast, molecular-based testing, such as reverse transcription polymerase chain reaction (RT-PCR), detects the transcript of PML/RARa gene rearrangement in virtually all samples of APL, even when karyotypic analysis is normal. The rapid nature of PCR-based testing, along with its high specificity and sensitivity profile, are significant advantages in the clinical setting. Because high complete response rates and relatively good overall survival rates are attained with the institution of appropriate combined therapy, treatment monitoring is an important aspect of APL management. A test that can accurately distinguish which patients will relapse from those that will remain in long-term remission would be of great value. Several studies have shown that RT-PCR is capable of meeting these standards. In the first three months after treatment or after ATRA therapy alone, the PCR test is not informative, since it remains positive. However, the PML/RARa RT-PCR assay has a high predictive value when used serially, beyond four months. For instance, in one series, a positive PCR result on two consecutive occasions predicted clinical relapse within a two to four month period, while a negative result was predictive of remission (up to five years follow-up). Moreover, patients with APL in long-term remission (up to 12 years) have also been shown to have negative PCR results, suggesting that an actual cure is achieved. This molecular test may potentially serve as a useful tool for determining the need for supplementary treatment during clinical remission. Although additional prospective studies are necessary to confirm these findings, PCR-based testing appears to be a reliable methodological approach for distinguishing cure from relapse in patients with APL. The goal of both current and future treatment protocols may well be a negative PCR test for PML/RARa gene rearrangement.

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