BCR-ABL1 Kinase Domain Mutation Analysis

Message

*Collect specimen Monday through Friday only before 1500 EST. Do not collect the day before a holiday.

Test Code

LAB00473

Alias/See Also

LAB00473
LabCorp TC: 480510
ABL1 Mutation Analysis for Resistance to Imatinib Mesylate
Gleevec Resistance Mutation Analysis
Imatinib Mesylate Resistance Analysis

CPT Codes
81170

Includes

Test code 480510 picks up the following mutations
T315I, T315A, V229L, Y253H, E225K, F359V, & F317L.

(T315I is not available individually.)

Preferred Specimen

5 mL Lavender (EDTA) - Whole Blood

Minimum Volume

3 mL Lavender (EDTA) - Whole Blood

Other Acceptable Specimens

Dark Green Top (Sodium Heparin) - Whole Blood
Yellow Top (ACD) - Whole Blood
1 mL Bone Marrow

Transport Temperature

Room Temperature

Specimen Stability

Room Temperature: 48 hours
If specimen has to be stored more than 48 hours, refrigerate at 2℃ to 8℃.

Reject Criteria (Eg, hemolysis? Lipemia? Thaw/Other?)

Specimen does not meet all of the above criteria for sample type, container, minimum volume, collection and storage; unsuitable specimens include but are not limited to: frozen whole blood or marrow; a leaking tube; clotted blood or marrow; a grossly hemolyzed specimen or otherwise visibly degraded; specimen suspected of being contaminated by another specimen; specimen contains specific foreign material.

Methodology
Polymerase Chain Reaction (PCR); direct sequencing; capillary electrophoresis

Report Available

10-14 days

Limitations

In vitro studies indicate that this analysis has a mutation detection sensitivity of ~20%. Mutations occuring outside of the analyzed region of the ABL kinase domain will also not be detected by this assay.
This test was developed and its performance characteristics determined by LabCorp. It has not been cleared or approved by the Food and Drug Administration.

Clinical Significance

Point mutations within the ABL1 kinase domain of the BCR-ABL1 fusion gene frequently cause secondary resistance to tyrosine kinase inhibitor (TKI) therapy. Those patients with a longer duration of CML prior to initiation of imatinib therapy are reported to have a higher incidence of detectable mutations compared to patients with an earlier onset of imatinib therapy. In addition, failure to achieve a major cytogenetic response within the first six months of therapy often reflects the presence of a mutation or a high probability that a mutation will subsequently be detected. Biochemical and cellular assays have demonstrated that the different BCR-ABL1 kinase domain mutations result in varying levels of resistance. Presence of kinase domain mutations are associated with poor prognosis and higher risk of disease progression. The different mutations may require differing strategies to overcome resistance, such as dose escalation, combination therapy or transplantation. Candidates for the BCR-ABL1 kinase domain mutation analysis include:

• Response milestones not reached

· Any sign of loss of hematologic response

· Any sign of loss of Complete cytogenetic response (CCyR) or its molecular response correlate-defined as an increase in BCR::ABL1 transcript to >1% International scale [IS]

· 1-log increase in BCR::ABL1 transcript levels and loss of Major Molecular Response (MMR)

• Disease progression to Accelerated Phase (AP-CML) or Blast Phase (BP-CML)

This assay sequences the entire ABL1 kinase domain and will detect all mutations in ABL1 kinase recommended by guidelines including G250E, Y253H, E255K/V, V299L, T315I/A, F317L/V/I/C, A337T, F359V/I/C and P465S.

Performing Laboratory
LabCorp

The CPT Codes provided in this document are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payor being billed. Any Profile/panel component may be ordered separately. Reflex tests are performed at an additional charge.