• Test Code:
    4080
  • Department:
  • 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) or yellow (ADC) tube (unspun)
  • 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 sample is to be shipped overnight, pour blood/bone marrow into RPMI media at a 1:1 ratio (1 mL of RPMI to 1 mL of blood/bone marrow) and mix thoroughly.
  • 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.  

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:

The Knight Cancer Institute at Oregon Health & Science University is a pioneer in the field of precision cancer medicine. The institute's director, Brian Druker, M.D., helped prove it was possible to shut down just the cells that enable cancer to grow. This breakthrough has made once-fatal forms of the disease manageable and transformed how cancer is treated. The OHSU Knight Cancer Institute is the only National Cancer Institute-designated Cancer Center between Sacramento and Seattle – an honor earned only by the nation's top cancer centers. It is headquarters for one of the National Cancer Institute's largest research collaboratives, SWOG, in addition to offering the latest treatments and technologies as well as hundreds of research studies and clinical trials.

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