• Test Code:
    4080
  • Department:
    Hematological Malignancies
  • Test Synonyms:
    BCR-ABL RNAPhiladelphia chromosome fusion transcript levels determinationBCR-ABL PCRCML monitoringCML minimal residual disease
  • CPT Code(s):
    8120681207
Background:

Chronic myeloid leukemia (CML) is a clonal hematologic stem cell malignancy associated, in greater than 90% of cases, with the Philadelphia chromosome (Ph), a reciprocal translocation between the long arms of chromosomes 9 and 22 [t(9;22)(q34;q11)].   The molecular consequences of the Philadelphia translocation are the physical juxtapositioning of sequences from the chromosome 22 BCR gene (breakpoint cluster region) adjacent to sequences from the chromosome 9 c-ABL gene encoding a non-receptor tyrosine kinase. 

The resulting BCR-ABL fusion gene is transcribed and translated into a 210 kD (p210) or 190 kD (p190) BCR-ABL fusion product with dysregulated (significantly enhanced) tyrosine kinase activity. 

The aberrant growth and differentiation of leukemic cells in CML is caused by the constitutive expression of the BCR-ABL kinase, a chimeric fusion protein resulting from a leukemia-specific chromosomal translocation described above.  Targeted inhibition of BCR-ABL with tyrosine kinase inhibitors (imatinib, dasatinib, nilotinib) is the standard treatment for CML (and Ph+ ALL).

The efficacy of TKI therapy is routinely monitored with serial BCR-ABL RNA PCR’s, which define the “molecular response”.   A consensus treatment goal is the achievement of “major molecular response”, a 3-log drop in BCR-ABL RNA, defined as 0.1% on the BCR-ABL RNA PCR international scale (IS) of measurement.

Clinical Utility:
The quantitative BCR-ABL RNA assay is intended to monitor the level of minimal residual disease in TKI-treated Philadelphia chromosome positive leukemias (CML or ALL). High or rising BCR-ABL RNA levels have been shown to increase the risk of leukemic relapse and drug-resistance mutations during TKI therapy. The failure to achieve a “major molecular response”, a 3-log drop in BCR-ABL RNA, defined as 0.1% on the BCR-ABL RNA PCR international scale (IS), is the consensus definition of a “sub-optimal” treatment that requires an alternative treatment approach. The OHSU BCR-ABL RNA PCR assay has been calibrated to the International Scale, and is one of only a few US assays reporting results on the IS.

Methodology:

By measuring BCR-ABL RNA levels using a sensitive real-time fluorescent PCR method, we are able to detect the presence of leukemic cells at a very low level.  The sensitivity limit of the assay is approximately 1 tumor cell in 100,000 normal cells.  A relative ratio (in percent) of BCR-ABL RNA to reference gene RNA is reported, as well as a value on the BCR-ABL international scale (which is the only way to assess major molecular response). 

Specimen Requirements:

  • Blood or Bone Marrow: 10-20 mL purple (EDTA)
  • Deliver to lab at shipping address above within 24 hours of collection, if sample cannot arrive within 24 hours, refrigerate until sample can be transported, then transport on ice packs; do not freeze.
  • If our lab is used to monitor the patient’s BCR-ABL1 RNA levels (by RQ-PCR), the same sample that was used for quantitative PCR can also be used for sequencing.We routinely store these samples (stabilized) for several weeks after RQ-PCR reporting.Please call Client Services at (855) 535-1522 to order sequencing.
  • RNA: 2ug (RNA must be extracted in a CLIA-certified laboratory or a laboratory meeting equivalent requirements as determined by the CAP and/or CMS)

A REQUISITION FORM MUST ACCOMPANY ALL SAMPLES.  Please include detailed clinical information.

Test Performed (Days):

Several times per week

Turn Around Time:

7-10 Days

Shipment Sensitivity Requirements:

  • Keep specimen cold during transit, but do not ship on dry ice. 
  • Contact Client Services for shipping kit and instructions at (855) 535-1522.  
  • Please use the cold pack provided in the KDL shipping kit. 
  • Ship the specimen overnight express, using the FedEx priority overnight label provided.
  • The specimen must arrive at the lab no more than 24 hours after collection.

References:

  1. Baccarani M, Cortes J, Pane F, et al. Chronic myeloid leukemia: an update of concepts and management recommendations of European LeukemiaNet. J Clin Oncol 2009;27:6041-6051.
  2. Baccarani M, Saglio G, Goldman J, et al. Evolving concepts in the management of chronic myeloid leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet. Blood 2006;108:1809-1820.
  3. National Comprehensive Cancer Network. NCCN: Clinical practice guidelines in oncology. Chronic Myelogenous Leukemia. Version 2. 2010. www.nccn.org.
  4. Press RD, Love Z, Tronnes AA, et al. BCR-ABL mRNA levels at and after the time of a complete cytogenetic response (CCR) predict the duration of CCR in imatinib mesylate-treated patients with CML. Blood 2006;107:4250-4256.
  5. Press RD, Galderisi C, Yang R, et al. A half-log increase in BCR-ABL RNA predicts a higher risk of relapse in patients with chronic myeloid leukemia with an imatinib-induced complete cytogenetic response. Clin Cancer Res 2007;13:6136-6143.
  6. Press RD, Willis SG, Laudadio J, et al. Determining the rise in BCR-ABL RNA that optimally predicts a kinase domain mutation in patients with chronic myeloid leukemia on imatinib. Blood 2009;114:2598-2605.

Additional Info: