t(9;22) BCR/ABL1 RNA Quantification for Chronic Myeloid Leukemia / Acute Lymphoblastic Leukemia

Background

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

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  2. 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.
  3. 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.
  4. Lowenberg, B. 2004. Minimal residual disease in chronic myeloid leukemia. N. Engl. J. Med. 349: 1399-1401.
  5. 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.