BCR/ABL1, Qualitative, Diagnostic Assay
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
mRNA transcribed from BCR/ABL (fusion of the breakpoint cluster region gene [BCR] at chromosome 22q11 to the Abelson gene [ABL] at chromosome 9q23) is detected in all chronic myelogenous leukemia (CML) patients and a subset of both acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) patients. Although breakpoints in the BCR and ABL genes may occur in a variety of locations, splicing of the primary RNA transcripts result in only 8 fusion site variants (e1/a2, e6/a2, e13/a2, e14/as, e19/a2, e1/a3, e13/a3, e14/a3) which incorporate the entire sequence of the exons on both sides of the fusion site. Although not reported in the literature, additional fusion variants (e20/a2, e6/a3, e12/a3, e19/a3, e20/a3) could theoretically result in disease-promoting bcr/abl proteins. Very rare, single-case reports of patients with fusions sites within the exons of BCR or ABL are also present in the literature.
In CML, >95% of patients have either an e13/a2 or e14/a2 fusion, both of which produce a 210-kDa protein (p210). More than 50% of patients with BCR/ABL-positive ALL have the e1/a2 fusion, which produces a 190-kDa protein (p190), and the majority of the remaining patients have either the e13/a2 or e14/a2 variants. Other fusions are very rare in any of the neoplasms known to harbor BCR/ABL.
When looking for the presence of mRNA from BCR/ABL (bcr/abl) at the time of diagnosis, it is important to use an assay that detects as many of the fusions as possible and identifies which fusion is present. This avoids false-negative results at diagnosis and assures the test subsequently selected for monitoring during therapy will detect the appropriate fusion product in each patient. This assay is designed to detect essentially all reported and theoretical BCR/ABL mRNA fusion variants.
Aids in the diagnostic workup for patients with bcr/abl-positive neoplasms, predominantly chronic myeloid leukemia and acute lymphocytic leukemia
When positive, the test identifies which mRNA fusion variant is present to guide selection of an appropriate monitoring assay.
If a quantitative monitoring assay is not available for a rare fusion variant, this assay may be of some value for monitoring, as it is quite sensitive and can provide a positive or negative result.
An interpretive report will be provided.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
This test is only qualitative and should not be used for routine (ie, quantitative mRNA level) monitoring. Monitoring of most chronic myeloid leukemia (CML) patients should be performed using BCRAB / BCR/ABL, p210 mRNA Detection, Reverse Transcription-PCR (RT-PCR), Quantitative, Monitoring Chronic Myelogenous Leukemia (CML). Monitoring of patients known to carry a p190 fusion should be performed using BA190 / BCR/ABL, p190, mRNA Detection, Reverse Transcription-PCR (RT-PCR), Quantitative, Monitoring Assay. If a patient is known to have a rare fusion variant that is not covered by 1 of these monitoring assays, contact Dr. He or Dr. Viswanatha at 800-533-1710 extension 6-5323 to discuss whether this qualitative assay can be used for 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.
A qualitative result is provided that indicates the presence or absence of BCR/ABL mRNA. When positive, the fusion variant is also reported.
Clinical References Provides recommendations for further in-depth reading of a clinical nature
1. Burmeister T, Reinhardt R: A multiplex PCR for improved detection of typical and atypical BCR-ABL fusion transcripts. Leuk Res 2008 Apr;32(4):579-585
2. Melo JV: The diversity of BCR-ABL fusion proteins and their relationship to leukemia phenotype. Blood 1996;88(7):2375-2384
3. Melo JV: BCR-ABL gene variants. Baillieres Clin Haematol 1997;10(2):203-222