The t(9;22) translocation is seen in cases of chronic myeloid leukemia (CML), a subset of acute lymphocytic
leukemia (ALL) and rarely in acute myeloid leukemia (AML). The resulting BCR-ABL fusion gene is transcribed and
translated into a 210 kD (p210, major transcript) or 190 kD (p190, minor transcript) BCR-ABL fusion product with
dysregulated (significantly enhanced) tyrosine kinase activity. Detection of the BCR/ABL1 fusion gene transcript
is a critical determinant in diagnosis. The BCR/ABL1 fusion gene product is the cause of disease and growth of
leukemic cells and expression levels of the transcript are directly related to disease severity. The use of new
drugs for treatment such as the tyrosine kinase inhibitor imatinib mesylate (Gleevec) reduces the amount of leukemic
cells below the level of cytogenetic detection and therefore makes molecular determination in the detection of minimal
residual disease desirable. A consensus treatment goal is the achievement of "major molecular response", a 3-log drop
in BCR-ABL RNA.
Clinical Utility
The test is done on peripheral blood or bone marrow specimens for confirmation of clinical diagnosis and monitoring of
treatment efficacy.
Methodology
The "major" breakpoint fusions occurring at either exon 13 or exon 14 of the BCR gene and/or the "minor" breakpoint
fusion at BCR exon 1 and ABL1 exon 2 are assessed. We quantify transcript levels using relative quantification using a
homogeneous cell line (K562 or SupB15) as the calibrator. The major breakpoint expression is calibrated to the
International Scale.
Specimen Required
Peripheral Blood: 3-5 ml, collected in EDTA (purple top) tube, store at room temperature 24 hours
Bone Marrow: 0.5-1 ml, collected in EDTA (purple top) tube, store at room temperature, 24 hours
Unacceptable Specimens: Frozen blood or bone marrow specimens are unacceptable as are tissue samples
that have undergone a freeze/thaw cycle(s).
Performed
Twice a week
Reported
Within 3-7 business days of receipt
CPT
BCR/ABL1 Gene Major 81206; BCR/ABL1 Gene Minor 81207
Shipment must include
Specimen
Requisition form
Patient pathology report
References
Aerts, J.L., M.I. Gonzales and S.L. Topalian. 2004. Selection of appropriate control genes to assess expression of
tumor antigens using real-time RT-PCR. BioTechniques 36: 84-91.
Gabert, J., E. Beillard, V.H.J. van der Velden, W. Bi, D. Grimwade, N. Pallisgaard, G. Barnaby, G. Cazzaniga, J.M.
Cayuela, H. Cave, F. Pane, J.L.E. Aerts D. De Micheli, X. Thirion, V. Pradel, M. Gonzalez, S. Viehmann, M. Malec, G.
Saglio and J.J.M. van Dongen. 2003. Standardization and quality control studies of "real-time" quantitative reverse transcriptase
polymerase chain reaction of fusion gene transcripts for residual disease detection in leukemia – A Europe Against Cancer
Program. Leukemia 17: 2318-2357.
Livak, K.J. and T.D. Schmittgen. 2001. Analysis of relative gene expression data using real-time quantitative PCR
and the 2−ΔΔCT method. Methods 25: 402-408.
Lowenberg, B. 2004. Minimal residual disease in chronic myeloid leukemia. N. Engl. J. Med. 349: 1399-1401.
Zhen, C.J. and Y.L. Wang. 2013. Molecular monitoring of chronic myeloid leukemia International standardization of
BCR-ABL1 quantitation. J. Molec. Diag 15: 556-564.